车前子提取物通过调控PI3K/AKT通路改善糖尿病大鼠神经源性膀胱病的作用研究

doi:10.12092/j.issn.1009-2501.2019.11.006

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (11): 1249-1255.doi: 10.12092/j.issn.1009-2501.2019.11.006

车前子提取物通过调控PI3K/AKT通路改善糖尿病大鼠神经源性膀胱病的作用研究

张恒，吴海啸，胡洋，杨庆，黄汀

浙江省金华市中心医院泌尿外科，金华 321000，浙江

收稿日期:2019-05-21 修回日期:2019-09-27 出版日期:2019-11-26 发布日期:2019-12-02
作者简介:张恒，男，硕士，主治医师，研究方向：泌尿系肿瘤。 Tel：15067596266 E-mail：vxlrvp@163.com
基金资助:
浙江省医药卫生科技计划项目（ZDA027）

Study on the improvement of PI3K/AKT pathway in diabetic rats with neurogenic bladder disease by extract of semen plantannical

ZHANG Heng, WU Haixiao, HU Yang, YANG Qing, HUANG Ting

Department of Urology, Jinhua Central Hospital of Zhejiang Province, Jinhua 321000, Zhejiang, China

Received:2019-05-21 Revised:2019-09-27 Online:2019-11-26 Published:2019-12-02

摘要/Abstract

摘要：

目的:探讨车前子提取物对糖尿病大鼠神经源性膀胱病的改善作用以及对PI3K/AKT通路的影响。方法:选取50只7周龄的SD大鼠，随机分为5组：对照组、模型组、低剂量组、中剂量组和高剂量组，每组10只，非对照组的4组进行糖尿病神经源性膀胱病的造模，观察4周，记录血糖、食量、尿量、饮水量、体质量等变化。造模完成后，低、中、高剂量组分别接受由低到高相应浓度为0.1、0.4、1.6 mg/mL的车前子提取物进行治疗，观察第5到第9周的血糖变化，第8和第9周的代谢以及第9周尿动力学指标的变化。荧光定量PCR和Western blot法检测PI3K/AKT通路相关基因的表达情况。结果:与对照组相比，模型组从造模后第1周开始血糖含量高于对照组（P<0.05），随后的3周血糖含量仍然高于对照组（P<0.05）。在第3周和第4周模型组的食量、饮水量和尿量均高于对照组（P<0.05），体质量从第1周开始低于对照组（P<0.05）。第9周的时候中、高剂量组的血糖水平恢复到正常水平，与对照组比较无统计学差异（P>0.05），高剂量组在食量、饮水量、尿量以及尿动力学方面已趋近于正常水平，与对照组比较无统计学差异（P>0.05）。与对照组相比，模型组、低剂量组和中剂量组的PI3K、AKT、p-PI3K、p-AKT的表达量均较低（P<0.05），高剂量组与对照组相比差异无统计学意义（P>0.05）。结论:一定剂量的车前子提取物可以调节PI3K/AKT通路中相关因子的表达，对糖尿病大鼠神经源性膀胱病有明显的改善作用。

关键词: 车前子提取物, PI3K/AKT通路, 糖尿病大鼠, 神经源性膀胱病

Abstract:

AIM: To investigate the effects of semen plantain extract on the improvement of neurogenic bladder disease in diabetic rats and the PI3K/AKT pathway. METHODS: Fifty SD rats of the same weight and age were randomly divided into 5 groups, the control group, model group, low dose group, middle dose group and high dose group, 10 in each group. Model group and dosage groups were built of diabetic neurogenic bladder disease model. The blood glucose, food intake, urine volume change, water quantity, and weight were recorded and observed after 4 weeks. After the completion of the model, the low-dose, medium-dose and high-dose groups were treated with plantago extract at the corresponding concentrations from low to high respectively, and the changes in blood glucose from week 5 to 9, metabolism indexes from week 8 and 9, and urodynamic indexes from week 9 were observed. Fluorescence quantitative PCR and Western blot were used to detect the expression of genes related to the PI3K/AKT pathway. RESULTS:Compared with the control group, the blood glucose level in the model group was higher than that in the control group from the first week after modeling (P<0.05), and the blood glucose level in the following three weeks was still higher than those in the control group (P<0.05). At 3th week and 4th week, the food and water intake and urine in the model group was higher than those in the control group (P<0.05), and the body weight of 1st week was lower than that in the control group (P<0.05). At 9th week, the blood glucose level of the middle and high dose groups returned to normal level, and no statistical difference was found between the two groups (P>0.05). The blood glucose level of the high dose group was close to normal level in terms of food and water intake, urine volume and urodynamics, and no statistical difference was observed between the two groups (P>0.05). Compared with the control group, the expressions of PI3K, AKT, p-PI3K and p-AKT in the model group, the low-dose group and the middle-dose group were all significantly decreased (P<0.05), while the differences between the high-dose group and the control group were not significant (P>0.05). CONCLUSION: A certain dose of plantain seed extract can regulate the expression of precursors in the PI3K/AKT pathway, and has significant improvement on neurogenic bladder disease in diabetic rats.

Key words: semen plantaginis extract, PI3K/AKT pathway, diabetic rats, neurogenic bladder disease

中图分类号:

张恒，吴海啸，胡洋，杨庆，黄汀. 车前子提取物通过调控PI3K/AKT通路改善糖尿病大鼠神经源性膀胱病的作用研究[J]. 中国临床药理学与治疗学, 2019, 24(11): 1249-1255.

ZHANG Heng, WU Haixiao, HU Yang, YANG Qing, HUANG Ting. Study on the improvement of PI3K/AKT pathway in diabetic rats with neurogenic bladder disease by extract of semen plantannical[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(11): 1249-1255.

参考文献

［1］Divino V, Boye KS, Lebrec J, et al. GLP-1 RA treatment and dosing patterns among type 2 diabetes patients in six countries: A retrospective analysis of pharmacy claims data［J］. Diabetes Ther, 2019,10(3):1067-1088.
［2］Ohmura H, Mita T, Matsuoka J, et al. Real-world data on the incidence of macrovascular complications in Japanese patients with type 2 diabetes: The sitagliptin registration type 2 diabetesjuntendo collaborating project［J］. Diabetes Ther, 2019,10(3):1099-1011.
［3］Takemura K, Takazawa R, Kohno Y, et al. Vesical fungus balls (fungal bezoars) by Candida albicans mimicking urothelial carcinoma in a patient with diabetic neurogenic bladder［J］. Urol Case Rep, 2018, 18:50-51.
［4］Niu X, Wang X, Huang H, et al. Bulbocavernosus reflex test for diagnosis of pudendal nerve injury in female patients with diabetic neurogenic bladder［J］. Aging Dis, 2016,7(6):715-720.
［5］Nayar S, Pawar B, Einsiedel L, et al. Isolated neurogenic bladder associated with human T-lymphotropic virus type 1 infection in a renal transplant patient from central Australia: A case report［J］.Transplant Proc, 2018, 50(10):3940-3942.
［6］Fukuda T, Bouchi R, Minami I, et al. Retrograde pyelonephritis and lumbar spondylitis as a result of Salmonella typhi in a type 2 diabetes patient with neurogenic bladder［J］. J Diabetes Investig, 2016, 7(3):436-439.
［7］李冲冲, 龚苏晓, 许浚, 等. 车前子化学成分与药理作用研究进展及质量标志物预测分析［J］. 中草药, 2018,49 (6):1233-1246.
［8］张居卫, 张建顺, 张海英. 车前子醇提取物对不同糖尿病模型小鼠降血糖效果的评价［J］.中国基层医药, 2015, (12):32-33.
［9］Vernstrom L, Laugesen E, Grove EL,et al. Differential vascular effects of aspirin in people with Type 2 diabetes without cardiovascular disease and matched controls without diabetes［J］. Diabet Med, 2019. doi: 10.1111/dme.13978.
［10］Gianatti EJ, Grossmann M. Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment［J］. Diabet Med, 2019. doi: 10.1111/dme.13977.
［11］Hertroijs DFL, Elissen AMJ, Brouwers MCGJ,et al. Preferences of people with Type 2 diabetes for diabetes care: a discrete choice experiment［J］. Diabet Med, 2019, 29(7):869-877.
［12］Hulls CM, Lentle RG, King QM, et al. Pharmacological modulation of the spatiotemporal disposition of micromotions in the intact resting urinary bladder of the rabbit; their pattern is under both myogenic and autonomic control［J］. BJU Int, 2019,123:S54-64.
［13］Wade D, Cooper J, Derry F, et al. Uro-Vaxom versus placebo for the prevention of recurrent symptomatic urinary tract infections in participants with chronic neurogenic bladder dysfunction: a randomised controlled feasibility study［J］. Trial,2019, 20(1):223.
［14］Bragge P, Guy S, Boulet M,et al. A systematic review of the content and quality of clinical practice guidelines for management of the neurogenic bladder following spinal cord injury［J］. Spinal Cord, 2019.doi: 10.1038/s41393-019-0278-0.
［15］Kang SH, Oh SJ, Jeong SJ, et al. Linguistic validation of the intermittent self-catheterization questionnaire for patients with neurogenic bladder who perform intermittent catheterization for voiding dysfunction［J］. Int Neurourol J, 2019, 23(1):75-85.
［16］Magarifuchi H, Kusaba K, Yamakuchi H, et al. Staphylococcus saprophyticus native valve endocarditis in a diabetic patient with neurogenic bladder: A case report［J］. J Infect Chemother, 2015, 21(9):695-699.
［17］Powell CR. Is the diabetic bladder a neurogenic bladder? Evidence from the literature［J］. Curr Bladder Dysfunct Rep, 2014, 9(4):261-267.
［18］张然, 袁从英, 冯娜, 等. 车前子多糖对糖尿病小鼠氧化应激的影响［J］. 天津医药，2011，39(3): 253-255.
［19］Chen L, Gong HY, Xu L. PVT1 protects diabetic peripheral neuropathy via PI3K/AKT pathway［J］. Eur Rev Med Pharmacol Sci, 2018, 22(20):6905-6911.
［20］Wang W, Li P, Xu J, et al. Resveratrol attenuates high glucose-induced nucleus pulposus cell apoptosis and senescence through activating the ROS-mediated PI3K/Akt pathway［J］. Biosci Rep, 2018, 38(2). pii: BSR20171454. doi: 10.1042/BSR20171454.

[1]	熊飞，施嫣嫣，沈久成，程洪兰，杭永付. 华蟾素对肺癌NCI-A549移植瘤裸鼠的抑制作用及机制研究[J]. 中国临床药理学与治疗学, 2018, 23(10): 1103-1108.
[2]	许文奇, 李先伟, 郝伟, 刘艳, 杨解人. 红杉醇对2型糖尿病大鼠心肌NADPH氧化酶亚单位p22phox、p47phox及iNOS蛋白表达的影响[J]. 中国临床药理学与治疗学, 2014, 19(6): 626-631.
[3]	郑建雷, 陈秋静, 陆林, 张奇, 张瑞岩, 沈卫峰. 阿托伐他汀对高脂饮食糖尿病大鼠主动脉几丁质酶-3样蛋白-1表达的影响[J]. 中国临床药理学与治疗学, 2014, 19(2): 133-138.
[4]	汤喜兰, 唐剑彬, 张启云, 董伟, 熊友文, 李冰涛, 徐国良. 黄连总生物碱对糖尿病大鼠降血糖作用研究[J]. 中国临床药理学与治疗学, 2010, 15(9): 967-971.
[5]	符丽娟, 王洪新, 庞东渤, 李艳芹. 氨基胍对糖尿病大鼠心脏功能及心肌超微结构的影响[J]. 中国临床药理学与治疗学, 2004, 9(9): 1037-1040.
[6]	闻智鸣. 不同剂量和不同给药次数的链脲霉素对大鼠胰岛的影响[J]. 中国临床药理学与治疗学, 2004, 9(10): 1128-1133.

车前子提取物通过调控PI3K/AKT通路改善糖尿病大鼠神经源性膀胱病的作用研究

Study on the improvement of PI3K/AKT pathway in diabetic rats with neurogenic bladder disease by extract of semen plantannical

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

本文评价