中药益肾颗粒通过PI3k/Akt/mTOR和LKB1/AMPK/Sirt1信号通路对糖尿病肾病大鼠的干预作用研究

Intervention effects of Yishen Granules on rats with diabetic nephropathy via PI3k/Akt/mTOR and LKB1/AMPK/Sirt1 pathways

目的:观察益肾颗粒对糖尿病肾病大鼠模型的干预作用。方法:105只大鼠随机选取10只为正常组,其余大鼠采用高糖高脂饲料喂养联合链脲佐菌素(STZ)小剂量腹腔注射诱导糖尿病肾病大鼠模型,造模成功后随机分为模型组、缬沙坦组(10mg/kg)、二甲双胍组(100mg/kg)及中药低、中、高剂量组(0.89、1.78、3.56g/kg),每组15只。灌胃10周后,检测血、尿、肾组织病理及相关蛋白的表达。结果:与模型组比较,益肾颗粒可以降低糖尿病肾病大鼠血肌酐(SCr)、尿素氮(BUN)、空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、24h尿蛋白定量等指标(P<0.05,P<0.01),减轻肾脏病理改变,降低PI3k、p-Akt、p-m TOR蛋白表达,升高LKB1、p-AMPK、p-Sirt1蛋白表达,以中药中剂量组改变尤为明显(P<0.01)。结论:中药益肾颗粒可能通过调节PI3k/Akt/m TOR和LKB1/AMPK/Sirt1信号通路,减轻糖尿病肾病大鼠肾脏病理改变。

Objective： To observe the intervention effects of Yishen Granules on diabetic nephropathy rat model. Methods： Diabetic nephropathy（DN） rat model was induced by high-sugar and high-fat diet combined with low-dose of Streptozotocin（STZ） intraperitoneal injection. After 10 weeks treatment, blood and 24 hours urine were collected, renal pathology was examined. The expressions of relative proteins were detected by Western blot. Results： Compared with the model group, Yishen Granule could reduce the serum creatinine（SCr）, urea nitrogen（BUN）, fasting blood glucose（FBG）, triglyceride（TG）, total cholesterol（TC） and 24-hour urine protein in DN rats（P〈0.05, P〈0.01）, and lighten the pathological changes of the kidney. The expression of PI3 k, p-Akt, and p-m TOR was decreased, while the expression of LKB1, p-AMPK, and p-Sirt1 were increased, especially in middle dose of Yishen Granules group（P〈0.01）. Conclusion： Yishen Granules can reduce SCr, BUN, FBG, TG, TC, and 24-hour urinary protein quantitative in DN rats. It may regulate the PI3 k/Akt/m TOR and LKB1/AMPK/Sirt1 signaling pathways to relieve the renal pathological changes of DN rats.