广州医药 ›› 2017, Vol. 48 ›› Issue (4): 12-16.DOI: 10.3969/j.issn.1000-8535.2017.04.003

• 论著 • 上一篇    下一篇

川芎嗪对STZ诱导2型糖尿病大鼠肾病TLR4表达的影响

傅永锦1, 刘艳波2, 潘竞锵1, 张小牧1, 吕俊华3   

  1. 1 广州市中医医院药学部(广州 510130)
    2 北华大学基础医学院病理生理学教研室(吉林 130021)
    3 暨南大学药学院药理学教研室(广州 510632)
  • 收稿日期:2017-03-13 发布日期:2021-12-01
  • 通讯作者: 潘竞锵,E-mail: pjq56@yahoo.com.cn
  • 基金资助:
    广东省科技计划项目(2013B21800034)

Effect of tetramethylpyrazine on the expression of TLR4 in type 2 diabetic nephropathy rats induced by STZ

FU Yongjin1, LIU Yanbo2, PAN Jingqiang1, ZHANG Xiaomu1, LV Junhua3   

  1. 1 Guangzhou Traditional Chinese Medical Hospital, Guangzhou 510130, China
    2 Department of Pathophysiology, School of Basic Medical Sciences, Beihua University,Jilin 132001,China
    3 Department of Pharmacology, Pharmacy College, Jinan University, Guangzhou 510632,China
  • Received:2017-03-13 Published:2021-12-01

摘要: 目的 探讨川芎嗪对链脲佐菌素(STZ)诱导2型糖尿病大鼠肾病的治疗作用及机制。方法 SD大鼠50只,随机分为正常组和模型组。除正常组外,其余大鼠均给予高脂-高糖饲料喂养4周,再给予链脲佐菌素(40 mg/kg,ip),72 h后测定空腹血糖,将血糖值高于16.67 mmol/L的大鼠随机分成4个组即模型组,二甲双胍阳性组(250 mg/kg),川芎嗪低、高剂量组(80、160 mg/kg),连续给予相应试药8周。其中正常组和模型组的大鼠均给予同等量蒸馏水灌胃。实验结束时,测定大鼠血糖、尿蛋白、血尿素氮和血肌酐含量;免疫组化法测定大鼠肾组织TLR4和caspase3蛋白表达。光镜下观察肾脏病理学变化。结果 与模型组比较,二甲双胍组和川芎嗪高剂量组给药8周后,大鼠动态空腹血糖均能明显降低(P<0.05),大鼠动态尿蛋白显著性降低(P<0.01,P<0.05); 二甲双胍和高剂量组TLR4和caspase3蛋白表达明显低于模型组(P<0.05);肾脏组织病理性损伤明显减轻。结论 川芎嗪对STZ诱导2型糖尿病大鼠肾病具有保护作用,其机制可能与下调TLR4表达作用有关。

关键词: 川芎嗪, 糖尿病肾病, TLR4, caspase3

Abstract: Objective To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP) on streptozocin(STZ)-induced-nephropathy in type 2 diabetic rats. Methods 50 SD rats were randomly divided into normal group(n=10) and model group(n=40). The model rats were fed on high fat and sugar diets for 4 weeks, then given STZ(40 mg/kg,ip). After 72 hours, the fasting blood glucose (FBG) was measured. Rats with high FBG above 16.67mmol/L were randomly divided into four groups: model, metformin(Met, 250 mg/kg)and TMP (80 mg/kg, 160 mg/kg) groups for treating 8 weeks, and both the control and model groups were given equals distilled water by intragastric administration. At the end of the experiment, blood glucose, urine protein, blood urea nitrogen and creatinine were measured. The expression of TLR4 and caspase3 protein in kidney tissue of rats was determined by immunohistochemistry. Pathological changes of kidney were observed under light microscope. Results Compared with the model group, metformin and high dose of TMP administered after 8 weeks, rats can significantly reduce the dynamic fasting blood glucose(P<0.05). Urinary protein excretion of total dynamic decreased significantly (P<0.01, P<0.05); the protein expression of TLR4 and caspase3 in the metformin group and high dose group was significantly lower than that in the model group (P<0.05); kidney tissue pathological damage was significantly reduced. Conclusion TMP has a protective effect on STZ induced nephropathy in type 2 diabetic rats, and its mechanism may be related to the down-regulation of TLR4 expression.

Key words: Tetramethylpyrazine, Diabetic nephropathy, TLR4, Caspase3