通心络超微粉联合津力达颗粒对糖尿病肾病大鼠Akt/mTOR信号转导通路的影响

目的:探讨通心络超微粉联合津力达颗粒对糖尿病肾病(DN)大鼠蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(m TOR)信号转导通路的影响。方法:将SD大鼠80只大鼠分为正常组,模型组,厄贝沙坦组(25 mg·kg~(-1)·d~(-1)),通心络超微粉组(0.8 g·kg~(-1)·d~(-1)),津力达颗粒组(1.5 g·kg~(-1)·d~(-1)),通心络超微粉加津力达颗粒组(0.8+1.5 g·kg~(-1)·d~(-1)),共6组;尾静脉注射链脲佐菌素建立糖尿病(DM)动物模型;采用免疫组化SP法测定肾组织中的血管内皮生长因子(VEGF)蛋白的表达;采用Western blot检测Akt/m TOR信号转导通路中Akt,m TOR蛋白及相应磷酸化蛋白p-Akt与p-m TOR的表达水平。结果:与正常组比较,模型组中VEGF蛋白的表达升高;各给药组中VEGF蛋白的表达与模型组比较均有不同程度降低,其中通心络超微粉加津力达颗粒组更接近于正常组;各组Akt及其下游分子m TOR的总蛋白表达水平无统计学差异,与正常组比较,模型组中p-Akt与p-m TOR蛋白的表达明显升高(P0.01),与模型组比较,各给药组则显著降低(P0.01)。结论:通心络超微粉联合津力达颗粒可抑制DN大鼠Akt/m TOR信号转导通路的活化,并致相关蛋白VEGF表达水平的降低。

Effects of Tongxinluo Submicron Powder Combined with Jinlida Granules on Akt/mTOR Signal Transduction Pathway in Rats with Diabetic Nephropathy

Objective: To study the effects of Tongxinluo submicron powder combined with Jinlida granules on protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signal transduction pathway in rats with diabetic nephropathy(DN). Method: The 80 SD rats were divided into normal group, model group, irbesartan group (25 mg · kg^-1 · d^-1), Tonxinluo submicron powder group(0.8 g · kg^-1 · d^-1), Jinlida granules group(1.5 g · kg^-1 · d^-1) and Tonxinluo plus Jinlida group(0.8+1.5 g · kg^-1 · d^-1). Rats were injected with streptozotocin (STZ) by tail intravenous injection to establish diabetes mellitus (DM) models. The expression of vascular endothelial growth factors (VEGF) in renal tissues was detected with immunohistochemical assay of SP. The expression of Akt and mTOR proteins in Akt/mTOR signal transduction pathway as well as the expression of corresponding phosphorylated proteins p-Akt and p-mTOR were detected by Western blot. Result: The expression of VEGF was significantly enhanced in model group compared with the normal group, and the expression of VEGF in various medication groups was weakened by different degrees compared with the model group. The results of Tongxinluo submicron powder plus Jinlida granules group were more close to the results in normal group. There were no statistical differences in total protein expression of Akt and downstream molecules mTOR between all groups;while the expression of p-Akt and p-mTOR was significantly enhanced in the model group compared with the normal group (P<0.01), and the expression was significantly reduced in various medication groups (P<0.01). Conclusion: Tongxinluo submicron powder combined with Jinlida granules could suppress the activation of Akt/mTOR signal transduction pathway and reduce the expression of VEGF of relevant proteins in rats with DN.