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Table of Content

    Volume 27 Issue 8
    26 August 2022
    Effects of rapamycin intervention during pregnancy on cognitive function of autism model in rat offspring
    Qin LiYang
    2022, 27(8):  841-847.  doi:10.12092/j.issn.1009-2501.2022.08.001
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    AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring.  METHODS: Fourteen pregnant rats were randomly divided into normal group (n=3), model group (n=4), rapamycin (RAPA) control group (n=3) and intervention group (n=4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P<0.05), while the indexes between the intervention group and model group were reversed (P<0.05). The model group had higher PWMT than normal group (P<0.01) and the PWMT of intervention group was lower than that of model group (P<0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P<0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P<0.01) and intervention group shifted to left compared with model group (P<0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P<0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P<0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.
    Experimental study of schisandrin B attenuates acute myocardial ischemia injury in rats by inhibiting cardiomyocyte apoptosis
    HUA Haiyan, YAN Jie, QIN Yufen
    2022, 27(8):  848-856.  doi:10.12092/j.issn.1009-2501.2022.08.002
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    AIM: To explore the protective effect and mechanism of schisandrin B (Sch B) on myocardial ischemia-reperfusion injury (MIRI) in rats.  METHODS: Forty SD rats were randomly divided into control group, MIRI group,MIRI+30 mg/kg Sch B (MIRI+L-Sch B) group and MIRI+60 mg/kg Sch B (MIRI+H-Sch B) group, ten in each group, Sch B were intragastrically for 7 days. Ligation of the left anterior descending branch was used to establish MIRI model, control group rats only underwent sham operation. The ardiac function parameters of ejection fraction (EF), fractional shortening (FS), maximum rate of increase in left ventricular pressure (+dp/dtmax), maximum rate of decline in left ventricular pressure (-dp/dtmax) values were recorded after 120 min reperfusion. CK-MB, LDH, cTnI activities in serum were detected. MPO, MDA and GSH-Px in myocardial tissue were detected. TTC, HE and TUNEL staining were used to detect myocardial infarction area, histopathological changes and cardiomyocyte apoptosis. Western blot was used to detect cleaved caspase 3, Bcl-2 and Bax protein in myocardial tissue. RESULTS: After Sch B pretreatment, the values of EF, FS, -dp/dtmax and levels GSH-PX in MIRI rats significantly increased (P<0.05 or P<0.01), while the activities of CK-MB, LDH, cTnI and MDA were significantly decreased (P<0.05 or P<0.01), myocardial infarction area significantly reduced (P<0.01), myocardial tissue damage was improved (P<0.01), cardiomyocyte apoptosis also reduced (P<0.05, P<0.01), cleaved caspase 3/caspase 3, Bax protein expression levels were significantly decreased (P<0.05 or P<0.01), Bcl-2 protein expression levels were significantly increased (P<0.05 or P<0.01); MIRI+H-Sch B group rats +dp The /dtmax value was significantly increased (P<0.05), and the MPO level was significantly decreased (P<0.01), shows dose-dependent effect.CONCLUSION: Pretreatment of Sch B attenuated MIRI-induced myocardial injury in rats, and its mechanism may related to inhibition oxidative stress, decreased cleaved caspase 3, Bax protein expression and increased Bcl-2 protein expression to inhibit cardiomyocyte apoptosis.
    Study on the treatment of thin endometrium with growth hormone and vitamin E
    DING Jiamin, WANG Youdi, ZHAO Xiali, JIANG Genfeng, CHEN Siwen, HONG Chengcheng, LI Shuqin, HU Weihua
    2022, 27(8):  857-862.  doi:10.12092/j.issn.1009-2501.2022.08.003
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    AIM: To study the effect of growth hormone (GH) and vitamin E (Vit.E) combined in the treatment of endometrial thinning.  METHODS: Twenty female SD rats were randomly divided into four groups: control group, model group, GH group and treatment group, with 5 rats in each group. Control group was routinely fed; Rats in model group, GH group and treatment group were injected intrauterine with 95%ethanol during estrus stage to construct a thin endometrial model. Six to eight hours after operation, rats in model group were injected intrauterine with 0.2 mL normal saline, rats in GH group and treatment group were injected with the same amount of GH, and the treatment group was given intragastric treatment of 60 mg/kg Vit.E. The rats were sacrificed 3 estrus cycles (about 2 weeks) after the operation. HE staining was performed on the uterine tissue to identify the model, and the levels of Cytokeratin 19 and Vimentin in the endometrium were detected by immunohistochemical color. RESULTS: The endometrial thickness of the model group was significantly thinner than that of the model group, and the endometrial thickness of the treatment group was significantly higher than that of the control group, but the endometrial thickness of the GH group was slightly lower than that of the control group. The expression levels of keratin and vimentin in model group were lower than those in GH group, control group and treatment group, and the differences were statistically significant. CONCLUSION: Endometrial-related proliferation indexes were significantly increased after GH and vitamin E treatment, and GH and vitamin E could effectively promote the proliferation of endometrial cells.
    Effect of COX-2 inhibitors on postoperative delirium in elderly patients undergoing orthopedic surgery and its possible mechanism
    WANG Jinhuo, GAO Xinyue, GUO Jianrong
    2022, 27(8):  863-869.  doi:10.12092/j.issn.1009-2501.2022.08.004
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    AIM: To observe the effects of cyclooxygenase-2 (COX-2) inhibitors on the levels of inflammatory factors, nerve damage-related factors and antioxidant factors, as well as pain and delirium scores in the plasma of elderly patients with orthopaedic surgery, to clarify the role of COX-2 inhibitors in the prevention and treatment of POD and explore its possible mechanism.  METHODS: Eighty patients undergoing elective hip arthroplasty were randomly divided into parecoxib sodium group (P group, n=40) and control group (C group, n=40). Group C was injected with the same volume of normal saline at the same time point, and the preoperative cognitive function was screened 1 d (T0) before surgery by MMSE scale. The occurrence of POD was determined by CAM-CR scale score 1 d before operation (T0), 1 d after operation (T4), 3 d after operation (T6), 5 d after operation (T7). 1 d before surgery (T0), 12 h after surgery (T3), 1 d after surgery (T4), 2 d after surgery (T5). VAS scale score was used to observe the pain degree 30 min before anesthesia (T1), 1 h after surgery (T2), 1 d after surgery (T4). Central venous blood was collected from internal jugular vein 3 days after operation (T6), and the contents of inflammatory factors (IL-6 and IL-10) nerve injury related factors (S-100β protein, NSE, BDNF) and antioxidant factors (HO-1) were determined by ELISA.RESULTS: There were no significant differences in general condition, MMSE score and inflammatory factors, nerve damage-related factors and antioxidant factors between 2 groups at T1 (P>0.05). At T2 and T4, IL-6, S-100β and NSE in group P were lower than those in group C, while IL-10, BDNF and HO-1 were higher than those in group C (P<0.05). At T6, s-100 β and NSE in group P were lower than those in group C, BDNF was higher than those in group C (P<0.05), and there were no significant differences in IL-6, IL-10 and HO-1 between the two groups (P>0.05). There were no significant differences in VAS and CAM-Cr scores between the two groups at T0 (P>0.05). VAS score of group P was lower than that of group C at T3, T4 and T5 (P<0.05). At T4, T6 and T7, the CAM-CR score of P group was lower than that of C group, and the POD incidence of P group was lower than that of C group (P<0.05). CONCLUSION: COX-2 inhibitor (Parecoxib) can relieve postoperative pain in elderly patients, reduce postoperative plasma inflammatory factors and nerve injury related factors, increase antioxidant level and reduce the incidence of POD. The mechanism of POD reduction may be related to its anti-inflammatory, analgesic and antioxidant effects.
    Individualized precision therapy for patients with ischemic stroke and hypertension
    FU Hong, TIAN Lei
    2022, 27(8):  870-876.  doi:10.12092/j.issn.1009-2501.2022.08.005
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    AIM: To investigate the influence of CYP3A5 gene polymorphism on the anti-hypertensive efficacy of calcium channel blocker in patients with ischemic stroke and hypertension. METHODS: A total of 108 cases of ischemic stroke patients with hypertension were included and divided into experimental group and control group, and 54 cases in each group, the experimental group selected amlodipine tablets and levamlodipine tablets respectively according to the results of genetic testing, while the control group selected amlodipine tablets, which in order to investigate the antihypertensive efficacy of the two groups. RESULTS: The effective rate of experimental group and control group was 77.78%and 57.41%(P<0.05). In the experimental group, the antihypertensive effect of GG and AG genotype patients after taking amlodipine tablets was significantly higher than that of AA type patients, and GG type patients had a stronger antihypertensive effect than AG type patients after taking amlodipine tablets. CONCLUSION: CYP3A5 gene polymorphism is very important for blood pressure control by calcium channel blockers in patients with ischemic stroke and hypertension.
    Research progress on pathogenic fusion gene in lung cancer
    WANG Lin, LI Chongyang, LI Shuaihu, GAO Shenghan, XU Tian, LI Fei
    2022, 27(8):  877-885.  doi:10.12092/j.issn.1009-2501.2022.08.006
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    Lung cancer is one of the most harmful global diseases with high morbidity and mortality rate. As a unique kind of driver gene, the pathogenic fusion gene is a common mechanism of lung cancer. Most fusion genes are produced by chromosome rearrangement and encoding receptor tyrosine kinases, which could be potential lung cancer therapeutic targets. Since ALK was first identified in 2007, methods like FISH, IHC, RT-PCR and NGS have been intensively applied, leading to identification of multiple other lung cancer fusion genes including ROS1, RET, FGFR, NTRK1, NRG1, DNAH5 and LTK. These works broaden the spectrum of lung cancer related gene mutations, and support the customized treatment for clinical patients. For some fusion genes, corresponding kinase inhibitors have been developed with good efficacy, however, the treatment is still being challenged by several problems like drug resistance. Based on recent studies, the research development of lung cancer fusion genes will be discussed.
    Research progress on the role and mechanism of irisin in organ ischemia/reperfusion injury
    HAN Xiaoxia, LENG Yufang, LV Xingjiao, HOU Xiaoyu, CAO Xuefen, Janvier NIBARUTA
    2022, 27(8):  886-891.  doi:10.12092/j.issn.1009-2501.2022.08.007
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    Irisin is an endogenous secreted muscle factor, which not only plays a certain clinical application value in a variety of metabolic diseases, cardiovascular and cerebrovascular diseases, neurological diseases, tumors and other diseases, but also affects the occurrence and development of organ ischemia/reperfusion injury. In this paper, the role and mechanism of irisin in organ ischemia/reperfusion injury were summarized, aiming to provide new ideas for prevention and treatment of organ ischemia/reperfusion injury.
    Research progress on experimental pharmacology models of sarcopenia from the view of senescence
    FU Yongfang, GUO Yixun, WANG Jing, LI Wenxiong, ZHANG Yan
    2022, 27(8):  892-898.  doi:10.12092/j.issn.1009-2501.2022.08.008
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    Sarcopenia, characterized as the progressive decrease in skeletal muscle mass, strength, and function, has been becoming one of chronic musculoskeletal diseases in aging people. In basic research studies, a reliable experimental model would be vital significance for deeply understanding pathophysiological mechanism of sarcopenia and developing novel drugs. This review provided a preliminary summary on the potential mechanisms involved in senescence-induced sarcopenia, followed by a discussion on research progress on pharmacology models based on molecular mechanism of senescence, especially from in vitro cell models and in vivo animal models.
    Research progress on chemistry and bioactivity of isopentenyl flavonoids from Sophora flavescens
    HE Xudong, FU Zhongyu, HUANG Ying, HE Jinbiao, PU Xuemei, LI Jie, LI Yanjuan, YU Jie, YANG Xingxin
    2022, 27(8):  899-907.  doi:10.12092/j.issn.1009-2501.2022.08.009
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    Isopentenyl flavonoids are a class of characteristic components in Sophora flavescens Ait. (S. flavescens). They have biological activities such as anti-tumor, anti-bacteria, anti-inflammol/Lation and anti-oxidation. In this paper, the structural types, toxicology and pharmacological effects of isopentenyl flavonoids from S. flavescens were briefly reviewed. Furthermore, the worth of further study on pharmacokinetics, pharmacodynamics, toxicology, action targets, molecular mechanisms and structure-function relationships of isopentenyl flavonoids were proposed. The deep exploration on functional characterastics of isopentenyl flavonoids of S. flavescens and their application on development of innovative drugs are of great significance to further improve the added value of isopentenyl flavonoids and expand their application fields.
    Pharmacokinetics and clinical significance of drugs for improving nonalcoholic fatty liver disease
    MA Shen, LIU Yushuo, TANG Hui, CHEN Wenbin, GAO Ling
    2022, 27(8):  908-918.  doi:10.12092/j.issn.1009-2501.2022.08.010
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    Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease in China. There is no specific drug approved for marketing at home and abroad. At present, some adjuvant drugs are mainly used to improve the progress of the disease. Being familiar with and mastering the pharmacokinetic characteristics is very important for the selection and use of drugs. According to the characteristics of drug absorption, distribution, metabolism and excretion, reasonable drugs are selected to improve the therapeutic effect and reduce adverse reactions. Therefore, this paper reviews the pharmacokinetics and clinical significance of drugs commonly used to improve nonalcoholic fatty liver disease in hope of providing basis for clinical medication.
    Research progress of exosomal miRNA in skin wound healing and regeneration
    MA A'xue, LU Xiaohong, DONG Bo, WANG Dong
    2022, 27(8):  919-924.  doi:10.12092/j.issn.1009-2501.2022.08.011
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    Skin is the largest organ of the human body, and maintaining the integrity of the skin is very important to maintain the normal function of the body. Repair and regeneration after skin trauma is a complex dynamic process, which involves biological processes such as cell proliferation and migration, extracellular matrix synthesis and deposition, angiogenesis and remodeling. Recently, exocrine miRNA is increasingly considered as a potential therapy for the treatment of skin trauma. Exosomes, as intercellular messengers, can affect the function of target cells through fusion, endocytosis and receptor-ligand interaction. MiRNA, the main component of exosomes, plays an important role in all stages of wound repair. Therefore, understanding the specific role of exocrine miRNA in skin wound repair and regeneration may provide a powerful basis for the development of new treatments for skin trauma in the future. In this review, we summarized the role of exocrine miRNA in the three stages of inflammation, proliferation and remodeling of skin wound repair and regeneration, and expounded its mechanism. In addition, we also discussed the current limitations and future prospects of the study of exocrine miRNA in skin wound repair and regeneration, in order to provide ideas for follow-up research.
    Role and research progress of CYP46A1 in neurodegenerative diseases
    DU Jie, ZHAO Tingting, WANG Dalong, CHEN Xiaodong, LIU Kexin, WU Jingjing
    2022, 27(8):  925-935.  doi:10.12092/j.issn.1009-2501.2022.08.012
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    Cytochrome P450 (CYP46A1) is a central neuro-specific metabolic enzyme that converts cholesterol into 24-hydroxycholesterol. This metabolic process is the main mechanism of cholesterol elimination in brain and is closely related to the occurrence and development of neurodegenerative diseases. This review focuses on the relationship between CYP46A1 and neurodegenerative diseases, from the aspects of regulatory mechanism of CYP46A1 enzyme, the relationship between CYP46A1 and cognitive dysfunction, epileptic encephalopathy, and CYP46A1 enzyme activity modifiers (inhibitors and agonists) to illustrate the pivotal role of CYP46A1 in the development and prevention of neurodegenerative diseases in hope of providing new target and direction for the research and development of new drugs.
    Advances in uridine diphosphate glucuronosyltransferase-mediated drug interactions with tyrosine kinase inhibitors
    HE Xueru, FU Yuhao, XUN Xuejiao, CUI Yanjun, DONG Zhanjun
    2022, 27(8):  936-945.  doi:10.12092/j.issn.1009-2501.2022.08.013
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    Drug-drug interactions (DDI) of tyrosine kinase inhibitors (TKIs) mediated by metabolic enzymes and transporters have become an important issue in clinical practice recently. In addition to CYP450 enzymes, uridine diphosphate glucuronidases (UGTs) are another class of metabolic enzymes involved in the metabolism of TKIs, and most TKIs can inhibit the UGTs in vitro. Potential clinically meaningful DDIs may occur with the coadministration of TKIs and substrates or inhibitors of UGTs. This paper will mainly focus on the UGTs-mediated drug-drug and the effect of UGT1A genotype on the drug interactions of TKIs and explores strategies to address, aiming to provide clinicians and pharmacists with references for the safe and rational application of TKIs.
    Regulatory mechanism of LDLR and research progress of its related diseases and drugs
    LI Miao, YU Qinwei, JIANG Zhenzhou, ZHANG Luyong,
    2022, 27(8):  946-954.  doi:10.12092/j.issn.1009-2501.2022.08.014
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    Cholesterol is an important lipid component in the body, which not only participates in the formation of cell membranes, but also is the raw material for the synthesis of bile acids and steroid hormones. Low density lipoprotein receptor (LDLR) is involved in cholesterol metabolism and plays an important role in maintaining the cholesterol homeostasis of organism cells. The expression of LDLR is precisely regulated by transcription, post-transcription and post-translation, and the imbalance of ldlr expression will lead to the occurrence and development of many diseases. In this paper, the molecular regulation mechanism of LDLR, the damage of target organs caused by the imbalance of LDLR expression and the research and development progress of drugs targeting LDLR are reviewed, which provides theoretical basis for further understanding of the progress of diseases related to lipid metabolism disorder and new insights for developing drugs targeting LDLR with more effective and less side effects.
    Research progress on the antitumor effect of nifurtimox
    WANG Yali, HUO Xulei, CHEN Feng, LI Shenglan, ZHENG Xiaohong, WANG Can, LI Wenbin
    2022, 27(8):  955-960.  doi:10.12092/j.issn.1009-2501.2022.08.015
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    Malignant tumor is a major health problem facing all mankind, we are in urgent need to develop more effective anti-tumor drugs. Nifurtimox is a kind of nitrofuran compound, which is widely used in the clinical treatment of Chagas' disease. Recently, the anti-tumor effect of nifurtimox has been found and valued. This review described the anti-tumor effect of nifurtimox and its molecular mechanism.That is, nifurtimox increases reactive oxygen species, induces cell cycle arrest and apoptosis of tumor cells, inhibits AKT phosphorylation. Because of the variety of effective antitumor mechanism of nifurtimox, we expect that the drug can be applied to the treatment of malignant tumor.
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    2022, 27(8):  956. 
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