川芎嗪对糖尿病大鼠肾损伤的保护作用及相关蛋白nephrin和podocin表达的影响

Effects of tetramethylpyrazine on the renal injury of rats and protein expressions of nephrin and podocin

目的:研究川芎嗪对高脂高糖饮食与链脲佐菌素(STZ)诱致大鼠肾脏损伤的保护作用及与相关蛋白nephrin,podocin表达的影响。方法 :将50只雄性大鼠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STZ(40 mg/kg,ip)注射,72h后测定空腹血糖,将血糖值大于16.67mmol/L的大鼠随机分为4组:模型组,二甲双胍组(250 mg/kg),川芎嗪低剂量组(80mg/kg)和高剂量组(160mg/kg),连续给药8周。末次给药后,收集24h尿液,测定尿蛋白含量;取血测定血糖、血肌酐、尿素氮变化;光镜下观察肾脏病理学变化;Western Blot方法检测肾组织nephrin、podocin蛋白表达水平。结果:模型大鼠血糖值明显高于正常对照组,尿蛋白含量、血肌酐、尿素氮含量亦明显升高,肾组织nephrin、podocin蛋白表达水平降低。低高剂量川芎嗪治疗8周后,明显改善血糖水平,降低尿蛋白含量、血肌酐和尿素氮含量;肾组织nephrin和podocin蛋白表达增加,肾脏组织病理性损伤明显减轻。结论:川芎嗪对高糖高脂饮食与STZ诱致糖尿病大鼠肾损伤具有保护作用,其机制可能与诱导nephrin,podocin表达增加有关。

Objective： To investigate the effects of Tetramethylpyrazine on renal injury in streptozotocin - induced - diabetic rats and protein expres- sions of nephrin and podocin. Methods： 50 rats were randomly divided into normal control group（ 10 rats） and model group.. All model rats were fed by high -fat diet for 4weeks and then injected with streptozotoein（ STZ, 40 mg/kg,ip） . Blood glucose level was measured 72 h af- ter STZ injection using a One - Touch glueometer. Rats with fasting blood glucose levels of above 16.67mmol/L were randomly divided into four groups ： model control, Mefformin （ 250 mg/kg） and Tetramethylpyrazine （ 80mg：/kg, 160 mg/kg） groups. All rats were treated for 8 weeks. At the end of experiment, urine was collected from the rats for 24 h to measure the urinary volume and protein. Blood was collected to detect the changes of Fasting blood glucose, creatinine, blood urea nitrogen. The pathological changes of the kidney were observed under optic microscope. Protein expressions of nephrin and podocin were determined by western blot analysis. Results： Compared with normal control, the level of fasting blood ~glucose in model group increased significantly（ P 〈 0.01 ）, urinary protein over 24h , creatinine, blood urea nitrogen also significantly increased（ P 〈0.01 ） ,and protein expressions of nephrin and podoein in kidney decreased significantly（ P 〈0.01 ）. Treated with Tetramethylpyrazine （ 80mg/kg, 160 mg/kg） for 8weeks, the level of fasting blood glucose was significantly improved（ P 〈 0.01 ）. urina- ry protein over 24h, creatinine and blood urea nitrogen were decreased（ P 〈 0.05 ） , protein expressions of nephrin and podocin were also en- hanced （P 〈 0.01 ）. Glomerular pathological changes were ameliorated. Conclusions： Tetramethylpyrazine has a protective effect on renal in- jury of diabetic rats induced by high -fat diet and streptozotocin, and its mechanisms may be related to induction of protein expressions of nephrin and podocin.