Table of Content

Volume 9 Issue 2
26 February 2004

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Molecular mechanism of protective effects of estrogen on cerebral ischemia

HUANG Qian, LU Ying-Qing

2004, 9(2):  121-124. 

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Estrogen has the protective effect on cerebral ischemia in various ways.It not only can improve the regional cerebral blood flow during ischemia and rescue the remaining neurons alive, but also can reduce the injury of ischemia-reperfusion.In this article, we enumerate at the molecular level that estrogen has the properties of inhibiting the expression of VCAM and cytokines like TNF-αin the ischemia region, educing the overload of calcium and cytotoxicity of EAA by modulating the calcium channels, and regulating related genes expression and anti-apoptosis.It is crucial for estrogen replacement therapy as a neutoprotectant clinically.

Choice of animal models of experiment pancreatitis in vivo

WANG Nian-Lin, CHEN Ken, WANG Hui

2004, 9(2):  125-129. 

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Various animal models of the experiment pancreatitis in vivo were described in this paper. Although these models were widely applied nowadays, the appropriate choice of available model from them should be suit to experimental design and duplicated easily.

Effects of iptakalim hydrochloride on glutamate receptors and spontaneous synaptic activities in rat hippocampal neurons

ZHANG Ying-Li, WANG Hai

2004, 9(2):  130-135. 

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AIM: To investigate the effects of iptakalim hydrochloride (Ipt) on glutamate receptors and spontaneous synaptic activities in rat hippocampal neurons.METHODS: The cultured hippocampal neurons from neonatal rats were served as preparation.The effects of Ipt on glutamate receptors and spontaneous synaptic activities were observed by using whole-cell recording technique .RESULTS: Different concentrations of Ipt (1-100 μmol·L^-1) suppressed the glutamate and NMDA induced currents of rat hippocampal neurons in a dose-dependent manner, and these inhibitory effects were antagonized by K_ATP blocker glibenclamide (30 μmol·L^-1).Ipt inhibited the sEPSCs in cultured rat hippocampus neurons, and decreased both the frequency and amplitude, with no effect on mEPSCs.CONCLUSION: Ipt can block the function of glutamate receptor and attenuate the glutamatergic transmission in cerebral neurons, and these effects may be related with K_ATP.

Antiviral activity of complex of Hypericum perforatum L extract and lysine hydrochloride on herpes virus

HU Ran, KU Bao-Shan, ZHANG Yong-He, JIA Yong-Rui, YAO Hai-Yan, DUAN Shu-Min

2004, 9(2):  136-139. 

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AIM: To study the antiviral effects of the complex of Hypericum perforatum L and lysine hydrochloride against herpes simplex virus type 1 and varicella-zoster virus (VZV), and to evaluate the LD50 of the complex in mice.METHODS: The cytotoxities to Vero cells and 2BS cells and the antiviral activities were evaluated by cytopathic effect (CPE) inhibition assay.ICR mice were administrated(ig) the complex (2 ∶1) to determine LD50.RESULTS: The complex significantly inhibited the CPE of HSV-1 and VZV.MIC ranged from 9.7 to 19.5 mg·L^-1, IC50 ranged from 6.8 to 9.7 mg·L^-1.LD50 of the complex with ratio 2 ∶1 was 11.7 g·kg^-1 with 95 % confidence interval of 6.5-17.2 g·kg^-1 in ICR mice.CONCLUSION: The complex of Hypericum perforatum L and lysine hydrochloride has good effects on inhibiting HSV-I and VZV in vitro.The complex (2 ∶1) is safe in mice.

Selective vasodilating action in small artery and its pharmacological mechanisms of novel antihypertensive drug iptakalim hydrochloride

JIA Guo-Dong, CUI Wen-Yu1, LONG Chao-Liang, LIU Guo-Shu, WANG Hai

2004, 9(2):  140-145. 

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AIM: To study the selective vasodilating action in small artery and its pharmacological mechanisms of the novel antihypertensive drug iptakalim hydrochloride (Ipt).METHODS: Differences of the vasodilating action of Ipt in big artery and small artery were studied using isolated rat tail artery helical strips and aortic rings, and the effects of Ipt on potassium currents in smooth muscle cells derived from rat tail artery were observed by using patch clamp technique.RESULTS: The vasodilating action of Ipt at 10^-7-10^-3 mol·L^-1 was observed in rat tail artery strips precontracted with potassium chloride (KCl) in a concentration-dependent manner, and the vasodilating action presented a partially endothelium-dependent character, but no significantly vasodilating effect was seen in rat aortic rings.Ipt-induced relaxation in tail artery was significantly greater in spontaneously hypertensive rat than that in normotensive rat, and the vasodilating action of Ipt in small artery could be markedly antagonized by glibenclamide (10 μmol·L^-1) which only inhibited ATP-sensitive potassium channels.Moreover, the potassium currents in smooth muscle cells derived from rat tail artery could be augmented by Ipt.CONCLUTION: The novel antihypertensive drug iptakalim hydrochloride has a selective vasodilating action in small artery, and it has major pharmacological characters of ATP-sensitive potassium channel openers.

Effects of pioglitazone on lipid and glucose metabolism in normal, hyperlipidemia and fatty model rats

LIU Chang-Xiao, WANG Rui-Zhi, LI Jing

2004, 9(2):  146-148. 

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AIM: To study the effects of pioglitazone on the metabolism of glucose and lipid in animals.METHODS: The antidiabetic effects of pioglitazone were examined in normal SD rats, hyperlipidemia Wistar rats induced by specific forage breeding and fatty model rats induced by subcutaneous injections of monosodium glutamate in newborn rats.RESULTS: When piglitazone (6,12, and 24mg·kg^-1) orally given to normal SD rats, serum trigliceride decreased significantly, however, serum glucose did not change.Serum trigliceride and serum non-esterified fatty acid also decreased strikingly by pioglitazone in hyperlipidemia rats, and serum glucose did not alter, either. In fatty model rats, serum glucose, trigliceride and non-esterified fatty acid were improved by pioglitatazone.CONCLUSION: pioglitazone shows different effects on lipid and glucose metabolism in normal, hyperlipidemia and fatty model rats.

Changes of hemodynamic parameters and plasma vascular active substances in dog circulation failures induced by cholinesterase inhibitor

LI Guang, LONG Chao-liang, MU Shao-Feng, CUI Wen-Yu, WANG Hai

2004, 9(2):  149-152. 

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AIM: To investigate the changes of hemodynamic parameters and plasma vascular active substances before and after treatment with neuronal nicotinic receptor antagonist mecamylamine or muscarinic receptor antagonist atropine against the circulation failures induced by the cholinesterase inhibitor DDV in dogs.METHODS: 20 male dogs were randomized into 4 groups:control ;treatment with mecamylamine ;treatment with atropine and treatment with mecamylamine and atropine at the dose ratio of 1 ∶10.Animals were given intramuscularly DDV, and when the mean blood pressure was decreased to 40-45 mmHg, the drugs were intramuscularly injected and the changes of hemodynamic parameters such as mean arterial pressure (MAP), +dp/dt_max, Vpm and-dp/dt_max and vascular active substances such as nitric oxide (NO), endothelin(ET) and 6-Keto-PG1αbefore and after treated 15 and 60 min were observed.RESULTS: In anesthetized dogs intoxicated with cholinesterase inhibitor DDV, the circulation failure was characterized by the significant decreases in hemodynamic parameters MAP, +dp/dt_max, Vpm and-dp dt max.The plasma vascular active substances NO, ET and 6-Keto-PGF1α were increased significantly.After treated with mecamylamine and atropine 15 min, all the hemodynamic parameters were increased markedly and all the three vascular active substances were decreased significantly.After treated 60min, all the parameters were almost resumed to the normal level.The therapeutic effects of combination of mecamylamine and atropine were much better than those of mecamylamine or atropine used separately.CONCLUSION: The levels of vascular active substances NO, ET and 6-Keto-PGF1αin plasma can reflect the severity of circulation failure.There were synergic effects between mecamylamine and atropine against circulation failures induced by DDV.

Effects of dehydroepiandrosterone on cognitive function in mice with chronic mild stress

BAO Long, YANG Nan, LIU Yan-Yong, ZUO Ping-Ping

2004, 9(2):  153-156. 

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AIM: To investigate the alteration of behavior, such as spontaneous movement, spatial memory ability and cholinergic M receptors in the brain of mice with chronic mild stress (CMS).And to determine whether dehydroepiandrosterone (DHEA) can reverse the cognitive impairment in this model.METHODS: Forty mice were divided into four groups:control group, CMS group, CMS + DHEA low dose (ip, DHEA 5mg·kg^-1 ·d^-1) group and CMS +DHEA high dose (ip,DHEA 20 mg·kg^-1·d^-1) group. Morris water maze procedure was used to determine the spatial memory ability and M receptor binding activity was measured with radioactivity assay by 3H-QNB.RESULTS: (1) After 3 weeks in CMS, the spontaneous movement test decreased, and the latency in Morris water maze obviously prolonged. Treating CMS mice with DHEA for 3 weeks could enhance spontaneous movement and latency declined.(2) Whereas the 3H-QNB binding ability to M receptor showed a significantly decrease in cerebral cortex and hippocampus of CMS mice (P<0.05).But decreased ability of M receptor binding was reversed by DHEA treatment in hippocampus (P<0.05).CONCLUSION: DHEA can alleviate the stress response and reverse cognitive impairment induced by CMS, and it may be concerned with the central cholinergic M receptors activity.The studies also show that the low dose of DHEA is better to the CMS model than high dose.

Experimental study on inhibitory effect of antihyper coagulability state enzyme of snake venom in different dosages in mice with Hepatocarcinoma

RUI Jing, CHENG Ming-Rong, XU Yong-Qiang, WEN Shang-Wu

2004, 9(2):  157-161. 

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AIM: To research the inhibitory effect of antihypercoagulability state enzyme (AHCSE) of snake venom in different dosages in mice with Hepatocarcinoma.METHODS: Hepatic cancer H22 model in mice was performed through subcutaneous inoculation of Right-Sidedness Axilla of BALB/C mice.Different dosages of AHCSE (1, 2, and 4 mg·kg^-1) were injected via abdominal cavity everyday for 10 days.When the tumor grew to 10 mm³, the weight, volume, percent inhibition of tumor, spleen index and the number and the component of white blood cells were observed.RESULTS: The middle and high dosages of AHCSE had obvious inhibition in hepatic cancer.It showed a significant dose-dependent relation in the effects of AHCSE on neoplastic weight, neoplastic volume and splenic index.There was a linear regression between the number of leucocytes and the splenic index.CONCLUSION: AHCSE of 2-4 mg·kg^-1 has significant inhibitory effect on tumor, and shows dose-related effect in mice with Hepatocarcinoma.Its mechanism is presumably associated with activating immune system.

Effect of sennoside on intestinal movement of mice and study of relevant mechanism

WU Yu-Qing, WANG Jing-Xia, ZHOU Cheng-Hua, ZHANG Hong-Quan

2004, 9(2):  162-165. 

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AIM: To investigate the effect of anthracenedione derivative-sennoside extracted from rhubarb on intestinal movement of mice and its mechanism.METHODS: The effect of sennoside on intestinal movement of mice was observed by moist dejection counting test.The levels of motilin and somatostatin in small intestine of mice were determinated by radioimmunoassay.The Na⁺-K⁺-ATPase activity of small intestinal mucosa was measured by spectroscopic analysis.RESULTS: Different dosage of sennoside enhanced the function of excreting dejection .Different dosage of sennoside elevated the levels of motilin, and reduced the content of somatostatin in small intestine of mice significantly.The Na⁺-K⁺-ATPase activity of small intestinal mucosa of mice in sennoside group was inhibited significantly.CONCLUSION: Sennoside can enhance the function of intestinal movement of mice by a mechanism of promoting excretion of motilin, lower the level of somatostatin in intestine and inhibit the Na⁺-K⁺-ATPase activity of small intestinal mucosa.

Cytotoxicity of oxidized low-density lipoprotein on PC12 cells

CAO Li, YIN Hong-Cao, ZHOU Li, WANG Yong-Jun

2004, 9(2):  166-170. 

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AIM: To investigate the cytotoxicity of oxidized low-density lipoprotein (oxLDL) on PC12 cells.METHODS: PC12 cells were applied to be a neuron model and exposed to oxLDL.Cell injury was evaluated by cell viability (MTT assay), cell lysis (LDH assay), DNA fragmentation (TUNEL assay) and Caspase-3 activity (Caspase assay).RESULTS: Most of PC12 cells treated with oxLDL showed cell lysis changes and a few cells showed apoptotic changes, observed with electromicroscopically .The cell viability decreased with the concentration of oxLDL increasing.As the concentration of oxLDL increased, LDH release, DNA fragmentation and Caspase-3 activity also increased.However, there was no significant alteration in untreated control cultures and LDL control.CONCLUSION: oxLDL, but not native LDL, resultes in a dose- and time-dependent neuron death including cell lysis and apoptosis in which Caspases-3 participates.

Study of somatostatin on enhancing chemosensitivity of carcinoma of gdllbladder cells in vitro

LI Ji-Yu, QUAN Zhi-Wei, ZHANG Qiang, LIU Jian-Wen

2004, 9(2):  171-176. 

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AIM: To explore the change of chemosensitivity of carcinoma of gdllbladder cells after treated with somatostatin.METHODS: Twenty-four hours after somatostatin given, gradient concentrations of Adriamycin were added and growth curve of carcinoma of gdllbladder cells was investigated.The inhibitory effects of Adriamycin plus somatostatin and adriamycin alone were compared .RESULTS: Concentration-dependent inhibition of cell growth was shown in carcinoma of gdllbladder cells in adriamycin group (P<0.01).Somatostatin was found to induce carcinoma of gdllbladder cells growth arrest in DNA-Synthesis phrase, i.e., S phrase.After treated with somatostatin, inhibition of adriamycin was enhanced compared with that in adriamycin alone group (P<0.01).CONCLUSION: Somatostatin can enhance the chemosensitivity of carcinoma of gdllbladder cells treating with adriamycin.

Comparison of energy metabolism on brain lacking oxygen between Salvia miltiorrhiza Bunge injection and Salvia przewalskii Maxim injection in mice

LUO Hui-Ying, CHENG Ti-Juan

2004, 9(2):  174-175. 

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AIM: To compare the influence of salvia miltiorrhiza Bunge njection (SMBI) and salvia przewalskii Maxim injection (SPMI) on energy metabolism of acute brain lacking oxygen.METHODS: The whole brain lacking oxygen model was made by injecting NaNO₂ in mice and then wrote down the existent time of mice and detected the contents of Na⁺-K⁺-ATPase, Ca²⁺-ATPase and lactic acid (LD) in the brain.RESULTS: SMBI and SPMI both significantly lengthened the existent time of mice with the whole brain lacking oxygen, decreased the contents of LD and increased the activity of ATPase in mice.In increasing the activity of ATPase, the influence of SPMI was more than that of SMBI (P<0.05), but there was no significant difference between two injections in decreasing the contents of LD (P >0.05).CONCLUSION: SMBI and SPMI have distinctive protection on energy metabolism of acute brain lacking oxygen.Both of them can lengthen the existent of mice, reduce the contents of LD in brain and increase the activity of ATPase, but SPMI is more excellent than SMBI in increasing the activity of ATPase.

Comparison of three assays of CAg detection on evaluation of praziquantel efficacy in treatment with patients with schistosomiasis Japonica

YIN Dong, CHEN Hong-Gen, XU Xue-Ping, YI Fang-Yi, JIANG Wei-Sheng, ZHENG Xiao-Jun, WANG Ya-Qun, GAO Xiao-Hei

2004, 9(2):  177-179. 

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AIM: To compare 3 different methods of detecting the circulating antigen (CAg) to evaluate the chemotherapeutic effect in treatment with patients with schistosomiasis Japonica by praziquantel.METHODS: Serum CAg was detected in patients by Dot-ELISA, Sandwich-ELISA and R-IHA, based on monoclonal antibody (MAb) JPG3.The reverse negative rates were analyzed at six months, one year and two years after treatment with praziquantel 50 mg·kg^-1 (one dosage).RESULTS: The reverse negative rates of CAg in serum treated with praziquantel were 75.8 %, 72.6 %and 43.5 %at six months (P<0.01), 83.9 %, 88.7 % and 71.0 % at one year (P<0.05), and 87.1 %, 95.2 % and 93.5 % at two years (P >0.05) by Dot-ELISA, Sandwich-ELISA and R-IHA, respectively.The geometric mean reciprocal titer (GMRT) in positive individuals declined constantly at six months, one year and two years.CONCLUSION: Dot-ELISA and Sandwich-ELISA are better than R-IHA in evaluation of chemotherapy effect of praziquantel at six months and one year, whereas Sandwich-ELISA is more objective than Dot-ELISA for reading results.All of three assays have no significant difference after two years of treatment.TheGMRT that reflects circulating antigen level can also assess the cure after chemotherapy with praziquantel to a certain extent.

Immune therapeutic effect of oral soluble chicken collagen type Ⅱon adjuvant arthritis in rats

LU Yan-Xu, CHEN Min-Zhu

2004, 9(2):  180-183. 

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AIM: To investigate the immune therapeutic effect of a small amount of oral soluble chicken collagen type Ⅱ (SCC Ⅱ) on adjuvant arthritis (AA) in rats.METHODS: The ConA-induced the proliferative responses of splenocytes, mesenteric lymph node cells(MLNCs) and peyer' s patche cells(PPCs), IL-1 and TNFαproductions in the supernatants of peritoneal macrophages(PMΥ) and synovial membrane cells (SMCs) combined with the changes of the indices such as ankle joint secondary inflammatory responses, thymus indices and so on in AA rats were assayed or observed.RESULTS: SCC Ⅱ(0.03, 0.30 and 3.00 mg·kg^-1·d^-1, d 12-18, ig) could improve the overreduced ConA-induced splenocyte proliferative responses, but further reduced those of MLNCs and PPCs, inhibited the IL-1 and TNFαproductions in PMΥand SMCs, and ameliorated the secondary inflammatory responses in AA rats.CONCLUSION: A small amount of oral SCC Ⅱ(ig) have the immunotherapeutic effect on AA in rats.

Activation of NF-κB and anti-inflammation mechanism of pyrrolidine dithiocarbamate in rats with acute colitis

CHEN Ken, LONG You-Ming, LAN Lei, ZHENG Jie-Shun, WANG Hui

2004, 9(2):  184-188. 

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AIM: To investigate DNA-binding activity of nuclear factor kappa B (NF-κB) and pyrrolidine dithiocarbamate (PDTC) anti-inflammation effect and mechanism in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats.METHODS: Acute colitis was induced by instilling TNBS ethanol into the lumen of the rat colon.Rats were randomized into PDTC-treat group (including group P10, P25, P50, P100), TNBS ethanol group and normal control group.The rats in PDTC-treated group were injected intraperitoneally with PDTC at the dosages of 10, 25, 50, and 100 mg·kg^-1, respectively.Rats were killed at 4 h after enema.Colonic inflammation, the ratio of wet dry weight andMPO, SOD, andMDA activity were detected.DNA-binding activity of NF-κB was assessed by EMSA.RESULTS: NF-κB activity in colon homogenate was increased markedly at acute colitis in rats.PDTC attenuates the development of rat colonic inflammation but not by reducing the NF-κB activity.CONCLUSION: NF-κB is activated in rats with acute colitis, which may be a mechanism of self-protection. PDTC can attenuate the development of inflammation.

Protection of compound Hippophae rhamnoids L-granule on ischemic injury in cultured rat cortical neurons

ZHANG Wen-Bin, CHENG Ti-Juan, GAO Li-Ping

2004, 9(2):  189-192. 

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AIM: To study the protection of compound Hippophae rhamnoides L-granule (CHRG) on ischemic injury induced by glutamic acid (Glu) in the cortical neurons of rat cultured in vitro and its relevant mechanism .METHODS: The cortical neurons of the newborn rats (1 d) were cultured and separated.The protective effects of CHRG on ischemic injury induced by Glu were observed.The survival rate of the neurons was measured by MTT method, the content of LDH in extra-cellular bathing media was measured by colorimetry as well as the content of MDA, the activity of SOD and GSH-Px in the homogenate of cortical cells.RESULTS: When cells were treated with Glu, the content of LDH and MDA increased and the activity of SOD and GSH-Px decreased significantly.The observed group treated with CHRG could effectively prevent these changes.CONCLUSION: The serum preparation of CHRG shows protective effects on the cortical neurons injury induced by Glu and the mechanism may be related to suppressing the generation of lipids peroxides and cleaning excessive free radicals.

Effects of arsenolite on leukotriene B4 and genic expression of 5-lipoxygenase in asthmatic mice

YAO Wei-Min, LIANG Biao, LIU Yu-Yu

2004, 9(2):  193-196. 

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AIM: To investigate the role of leukotriene B4 (LTB4) and the expression of 5-lipoxygenase (5-LO) in ovalbumin-induced asthmatic mice and study the effect of arsenolite on LTB4 and the expression of 5-LO in those mice as well as the mechanism of arsenolite inhibiting asthma.METHODS: The mice were challenged with saline or OVA and ig with saline, mung bean, dexamethasone or arsenolite (0.625, 1.25, 2.50, 5.00mg·kg^-1) twice daily for 3 days.The LTB4 of BALF was measured by ELISA and RT-PCR was used to detect the mRNA expression of 5-LO in pulmonary tissue.RESULTS: The levels of LTB4 in BALF and 5-LO mRNA expression in pulmonary tissue of asthmatic group significantly increased compared with normal group.The levels of LTB4 in BALF and 5-LO mRNA expression in lung tissue in groups treated with 4 doses arsenolite were significantly lower than those in asthmatic group.Moreover, the 5-LO mRNA in group As 5.00 was significantly lower than that in group As 0.625.CONCLUSION: The high level of LTB4 in BALF, up-regulation of 5-LO mRNA in pulmonary tissue play very important roles in bronchial asthma.Arsenolite can efficiently treat asthma.Its mechanism maybe partly relates to the decrease of LTB4 in airway and the inhibitions of the mRNA expression of 5-Lo in pulmonary tissue.

Effects of tetramethylpyrazine on expression of Bcl-2 and Fas proteins in myocardial injury induced by catecholamine in rats

LU Yi-Min, WAN Fu-Sheng, TANG San-Bao

2004, 9(2):  197-200. 

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AIM: To observe the influence of tetramethylpyrazine on the expression of Bcl-2 and Fas proteins in myocardial injury induced by catecholamine in rats.METHODS: 36 Wistar rats were divided into 3 groups: cardiac injury group (n =12), tetramethylpyrazine treated group (n =12) and control group (n =12).The rat cardiac injury was induced by the subcutaneous injection of isoproterenol (ISO, 5 mg·kg^-1·d^-1).Bcl-2 and Fas protein was identified by immunohistochemical technique and the mean optical density (OD) values of the positive fields of protein expression were quantitatively examined by image analysis system.RESULTS: The expression of Bcl-2 protein was increased significantly in the cardiac injury group and tetramethylpyrazine treated group as compared with that of the control group (P<0.01).There were no significant difference in the Bcl-2 protein expression between the tetramethylpyrazine treated group and cardiac injury group (P >0.05), but the expression of Fas protein was decreased significantly in the tetramthylpyrazine treated group as compared with that of the cardiac injury group (P<0.05).The protein expression ratio of Bcl-2 Fas was increased significantly in the tetramethylpyrazine treated group as compared with those of the cardiac injury group and the control group.The myocardium pathological damage was decreased significantly in the tetramethylpyrazine treated group.CONCLUSION: Tetramethylpyrazine can significantly inhibit the expression of pro-apoptotic Fas protein and raise the ratio of Bcl-2 Fas protein cardiomyocytes.

Relationship of structure and bacteriostasis of 2-(carboxymethoxyl) benzaldehyde benzoyl hydrazone or their complexes

MA Xing-Ming, LUO Yan-Ping, MA Bao-Cheng, YANG Ru-Dong

2004, 9(2):  201-203. 

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AIM: To study bacteriostasis activities of ligand (2-(carboxymethoxyl) benzaldehyde benzoyl hydrazone (H2L)) and their complexes.METHODS: Ligand H2L and their complexes were synthesized.The bacteriostasis activities of H2L and their complexes in vitro were tested with K-B method.RESULTS: 2-(carboxymethoxyl) benzaldehyde benzoyl hydrazone only showed bacteriostasis activities on Staphyloccus aureus and their complexes had dramatic bacteriostasis activity on Staphylococcus aureus, Escherichia coli, and Bacillus subtilis.Bacteriostasis ring diameter of Cu-complex was largest.CONCLUSION: Ligand H2L complexes have bacteriostasis activities in vitro.Bacteriostasis activities of Cu-complex are strongest among the complexes.

Evaluation of clinical effect of laozhiling oral liquid on vascular dementia

GAO Chang, WANG Jing-Zhou

2004, 9(2):  204-207. 

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AIM: To study the effect of laozhiling oral liquid (LZL) in treating vascular dementia.METHODS: Patients were randomly divided into two groups:39 patients in the LZL treated group and 32 patients in the control group treated by Jinnaduo injection with therapeutic course of 3 months.Changes of minimental state examination (MMSE), Hasegawa' s Dementia Scale (HDS),activity of daily living (ADL) scores and levels of Angiotensin Ⅱ(AngII), Arginine vesopresin (AVP) and P300PL in cerebrospinal fluid were observed.RESULTS: The total effective rates in the LZL and Jinnaduo group were 61.54 % and 59.38 %, respectively, which had no significant difference between the two groups(P >0.05). MMSE, HDS scores of patients and the concentration of AVP could be obviously elevated (P<0.01), but the scores of ADL and levels of AngII markedly decreased (P<0.01).CONCLUSION: LZL has definite effect in treating VD and its therapeutic mechanism may be related to the actions of improving the function of neuropeptides.

Bioequivalence of naftopidil capsule vs tablet in Chinese healthy male volunteers

NI Li, LI Jin-Heng, YU Hai-Cheng, CAO Xiao-Mei

2004, 9(2):  208-211. 

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AIM: To study the pharmacokinetics and relative bioavailability of naftopidil in healthy male volunteers .METHODS: The naftopidil concentrations in plasma were determined by HPLC.The test and reference formulations of naftopidil were given to 18 healthy male volunteers .The calibration curve was linearwithin the range of 1.6-400 μg·L^-1, r =1.The minimum detection limit was 1 μg·L^-1.The mean recovery rate was 85.2 % -89.9 %, RSDs of inter-day and intra-day were no more than 8.0 %.RESULTS: After a single oral dose of 50 mg naftopidil test capsules or reference tablets, the main pharmacokinetic parameters AUC_0-24:295.6±90.9 and 291.6±89.3 μg·L^-1 ·h-1 ;AUC_0-∞:320.0±97.2 and 318.0±98.3 μg·L^-1·h^-1 ;T_max:0.6±0.2 and 0.6±0.2 h ;C_max:129.1±60.7 and 138.3±72.5μg·L^-1 ;T1 2:5.9±1.7 and 6.4±2.1 h, respectively.The relative bioavailability F_0-24, F_0-∞ were 101.9±12.9 % and 101.2±12.3 %, respectively.CONCLUSION: No significant difference exists among the pharmacokinetic parameters for the test capsules and the reference tablets of naftopidil.The two formulations were bioequivalent.

Effects of selenium and Vitamin E in combination and separateness on lipid peroxidation and NO contents of hearts, livers, kidneys and serum in rats with hyperlipidemia

ZHOU Chun-Yang, RAN Li, ZHANG Xiang, XU Bin, CAI Chun-Yan, FAN Ping

2004, 9(2):  212-215. 

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AIM: To investigate the effects of selenium (Se)and vitamin E (VE)in combination and separateness on the peroxidation of hearts, livers, kidneys and serum in rats with hyperlipidemia.METHODS: Highfat- diet (HFD)was used to cause experimental hyperlipidemia rats.50 SD rats were divided into 5 groups:control group ;high-fat-diet (HFD)group ;HFD +0.4 mg·kg^-1Se ;HFD +250 mg·kg^-1 VE ;HFD +0.4 mg·kg^-1 Se⁺250 mg·kg^-1 VE, respectively.After 4 weeks, the MDA contents in hearts, livers, kidneys and serum were measured through thiobarbituric acid (TBA)method.The NO contents in these samples were assayed by NO kits.RESULTS: HFD caused hyperlipidemia, in comparison with the control group, triglyceride (TG)and very low density lipoprotein (VLDL-C)increased(P<0.05), so did total cholesterol and low density lipoprotein (P<0.01). Meanwhile, HFD strengthened the peroxidation in all of the tissues or serum (P<0.05).NO contents were reduced in hearts and livers, but increased in serum and kidneys by HFD.VE or Se in combination and separateness did fight against these effects (P<0.05 or P<0.01).Meanwhile, VE and or Se can increase the NO contents in all the experimental tissues, combined use of Se and VE are more effective.CONCLUSION: Se and or VE can decrease the peroxidation-related damage and modify the NO contents in experimental hyperlipidemia rats.

Effects of naloxone on β-endorphin during myocardial ischemia-reperfusion injury in rabbits

LU Zhong-Qiu, HU Guo-Xin, WANG Ming-Shan, CHEN Xing-Yan, QIU Xiang-Jun, HUANG Wei-Jia, CHENG Jun-Yan, CHEN Shou-Quan

2004, 9(2):  216-219. 

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AIM: To study the effects of naloxone on β-endorphin (β-EP) in plasma and myocardium homogenate during myocardial ischemia-reperfusion (I R) injury in rabbits.METHODS: 45 New Zealand rabbits were randomly assigned into 5 groups (5 rabbits in control group, and each 10 rabbits in ischemia group, naloxone protection group, naloxone treatment group and ischemiareperfusion group).Myocardial ischemia models andmyo- cardial ischemia-reperfusion injury models in rabbits were made by means of ligating the left anterior descending branch of coronary artery and then investigated the change of β-EP in plasma and myocardium homogenate during I R injury after the protection and treatment with naloxone (an antagonist of opiate receptor).The blood and myocardium homogenate were taken at different times in each group.The levels of β-EP were detected with radioimmunology method.RESULTS: The levels of β-EP in plasma began to decrease after 2 h of ischemia, which were strikingly different to those before ischemia(P<0.05), and the levels of β-EP in myocardium homogenate also decreased.Comparing with those before ischemia, the levels of β-EP increased significantly after I R injury (P<0.05 or P<0.01), whereas its levels began to decrease after 4 h of I R and had no significant difference in naloxone protection group(P >0.05), but the treatment group showed no significant change(P >0.05).The levels of β-EP in myocardium homogenate had no difference to those before ischemia in all of three groups.CONCLUSION: Naloxone may effectively reduce the levels of β-EP during myocardial ischemia and I R injury, which decrease the injury to blood vessel and myocardium.

Gender difference of pharmacokinetics of oral cyclosporin A in renal transplanted recipients

YU Ai-Rong, WU Xiao-Chun, LI Qing, XIN Hua-Wen, ZHONG Ming-Yuan, XIE Sen

2004, 9(2):  220-222. 

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AIM: To study the effects of gender difference on the pharmacokinetics of oral cyclosporin A in renal transplanted recipients.METHODS: The study included 21 male patients and 20 female patients treated with CsA at 6 mg·kg^-1 ·d^-1 for two weeks.Each patient was involved in pharmacokinetics of CsA by fluorescence polarization immunoassay.RESULTS: The pharmacokinetic parameters of CsA in male and female renal transplanted recipients were:tmax (h):2.9±1.0 and 2.2±0.9 ;C_max (mg·L^-1):1.0±0.4 and 0.9±0.5 ;C_min(mg·L^-1):0.20±0.09 and 0.17±0.11 ;T1 2(a) (h):0.8±0.6 and 0.7±0.5 ;T1 2(e) (h):3.0±1.2 and 2.8±0.8 ;AUC0-12 (mg·L^-1) ·h-1:5.5±1.4 and 4.5±1.7 ;CL F(L·h^-1):40±25 and 47±35, and V F(C)(L):159±108 and 172±92, respectively.CONCLUSION: There is gender difference of pharmacokinetics of oral cyclosporin A in renal transplanted recipients.

Changes of NO concentrations of different tissues and blood pressure in stress rats

YIN Yan-Ru

2004, 9(2):  223-225. 

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AIM: To study the changes of NO concentrations of different tissues in stress rats.METHODS: Add stimulation with experiments employed electric food-shock and noise of busser as stressor for 15 days in SD rats, NO concentrations and BP were measured.RESULTS: In stress group, BPs increased before and after stress stimulation, but decreased levels NO concentrations of plasma, and there was no detectable amounts of NO in auricle, ventricle, vessel and adrenal.In stress +L-arg group, BPs did not increase before and after stress stimulation, NO concentrations of plasma increased, but auricle, ventricle, vessel and adrenal maintained the concentrations of NO.CONCLUSION: The stress stimulation can increase BP and low NO concentration, and L-arg can resist the response.

Effects of diatrizoate on endothelin receptor A in cardiac myocytes of diabetic nephropathy SD rats

LI Jing-Rong, XIONG Shu-Dao, WANG Yuan-Hui, WU Jian-Bo, WEN Bo-Gui

2004, 9(2):  226-229. 

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AIM: To investigate the effects of diatrizoate on the expression of endothelin receptor A (ETAR) in cardiac myocyte of diabetic nephropathy SD rats.METHEDS: 32 male SD rats (220-280 g) were randomly divided into four groups:8 normal control rats (Con group) with sham surgeon operation ;the other 24 were diabetic rats which were induced by intraperitoneal streptozotocin (35 mg·kg^-1 body weight) at one dose after they were uninephrectomized for 2 weeks.At the end of the eighth week, the diabetic rats were divided into 3 groups at random:(DM group) ;diabetic rats plus diatrizoate injection (10 ml·kg^-1) through tail vein of rats (CM group) ;BQ123 treated group (BQ group) which were injected the BQ123 (1 mg·kg^-1) before being injected the diatrizoate, while the Con group were only given the sterile water.ETARwas examined by reverse transcription polymerase chain reaction (RT-PCR) and western blot.RESULTS: Both RT-PCR and Western blot analysis indicated that ETAR had been upregulated in CM, DM and BQ groups compared with that in Con group (P<0.05) ;especially in CM group.BQ123 could downregulate the expression of ETAR gene induced by diatrizoate .CONCLUSION: Increasing ETAR may affect cardiac function induced by radiocontrast media diatrizoate under diabetic nephropathy conditions.However, BQ123 can downregulate the expression of ETAR gene induced by radiocontrast media diatrizoate and improve cardiac function.

Protective effects of ligustrazine on renal damage of acute ischemia-reperfusion in mice

HUO Zhan-Yang, NIU Gui-Ping, LIU Xiao-Li

2004, 9(2):  230-233. 

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AIM: To investigate the effects of ligustrazine (LT)on renal damage of acute ischemia-reperfusion in mice.METHODS: The model of renal ischemiareperfusion in mice was established by clamping the right renal pedicel in situ for 30min before reperfusion of blood 15 min, 60 min, and 24 h.Treated the mice with LT100 mg·kg^-1 ip (ligustrazine group)and saline ip (control group)30 min before operation.The levels of serum creatinine (Scr), blood urea nitrogen (Bun), content of malondialdehyde (MDA)and the activity of superoxide dismutase (SOD)in serum and renal tissue, numbers of WBC adhesion in renal tissue and scores of tubules were detected.RESULTS: LT lowered significantly MDA content and scores of tubules, the number of WBC adhesion, the levels of Scr, BUN, and increased the activity of SOD in renal tissues and serum.CONCLUSION: Ligustrazine may protect the renal damage of acute ischemiareperfusion, and the mechanism is to antagonize the free radical injury and to inhibit WBC adhesion.

Simulation method on power and sample size calculation in related rate non-inferior trial

ZHANG Gao-Kui, YAO Chen, XIA Jie-Lai

2004, 9(2):  234-237. 

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AIM: To develop a method to calculate sample size for related rate non-inferior trial.METHODS: Design SAS Macrore to calculate sample size for related rate in non-inferior trial by simulation.RESULTS: Two SAS MACROs are developed, one for power estimation and another for sample size calculation.CONCLUSION: Simulation is a good selection in sample size calculation while there is no formula can be used.

Ethic review on adverse reaction of compound prescription of cnidium fruit in clinical trail

LIU Shen-Lin, XIONG Ning-Ning, LIU Fang, WANG Xiu-Qin, GAO Wei-Min

2004, 9(2):  238-240. 

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In the clinical trail phase II of compound prescription of cnidium fruit (containing volatile oil extracted form cnidium fruit), 11 cases out of 20 exhibited adverse reactions, such as dizziness, palpitation, sweating, choking sensation in chest, numbness in lips and tongue.After analyzing the relationship between the adverse reactions and the drug, the ethical review committees further examined the credibility of the ADR reports, the common features of the group from which adverse reactions arose, the influencing factors of adverse reactions, as well as the continuation of the trial with decreased dosage. Comparing with the expected benefits of functional impotence, other marked Chinese patent medicines, and the clinical acceptance, ADR unforeknowable and unpreventable, the risks of the trial drug were much greater. Consequently, ethical review committees made the decision of cessation of the trial.