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目的:探讨积雪草酸(AA)对糖尿病(DM)大鼠肾脏c-Jun氨基末端激酶(JNK)信号通路及足细胞的影响。方法:链脲佐菌素诱导糖尿病大鼠模型,将糖尿病大鼠随机分为糖尿病组(DM组)和AA干预组(AA组),并以正常组(NC组)作对照。干预8周后测各组血尿素氮(BUN)、肌酐(SCR)、尿白蛋白排泄率(UAER)、血糖、肾皮质超氧化物歧化酶(SOD)、丙二醛(MDA)水平;透射电镜观察足细胞超微结构;Western blot法测肾脏p-JNK、JNK蛋白的表达;免疫组化法测足细胞nephrin蛋白的表达。结果:与NC组比较,DM组血BUN、SCR、UAER、血糖均显著增加(均P<0.01);肾皮质MDA含量显著增加(P<0.05),SOD活性显著降低(P<0.05);透射电镜示:DM组足突增宽,肾小球基底膜增厚,系膜基质增多。肾脏p-JNK、JNK表达均显著增加(均P<0.01);nephrin的表达显著降低(P<0.01)。与DM组比较,AA组血BUN、SCR、UAER、MDA含量均显著降低(均P<0.05),SOD活性显著增加(P<0.05);足细胞超微结构明显改善;肾脏p-JNK、JNK表达均显著降低(均P<0.05);nephrin表达显著增加(P<0.05)。结论:AA可能通过抑制糖尿病大鼠JNK信号通路的活性、上调足细胞nephrin的表达而发挥对糖尿病大鼠肾的保护作用。
Aims: To investigate the effects of Asiatic acid (AA) on c-Jun N-terminal kinase (JNK) signal pathway and podocyte in diabetic rats. Methods: Diabetic rats were induced by streptozotocin. Diabetic rats were randomly divided into diabetes group (DM group) and AA intervention group (AA group), and normal group (NC group) was used as control. The levels of blood urea nitrogen (BUN), creatinine (SCR), urinary albumin excretion (UAER), blood glucose, renal cortical superoxide dismutase (SOD) and malondialdehyde (MDA) The ultrastructure of podocyte was observed by electron microscope. The expression of p-JNK and JNK protein in kidney was detected by Western blot. The nephrin protein expression in podocyte was detected by immunohistochemistry. Results: Compared with NC group, the levels of BUN, SCR, UAER and blood glucose in DM group increased significantly (all P <0.01); the content of MDA in renal cortex increased significantly (P <0.05) Electron microscopy showed: DM group foot process widens, glomerular basement membrane thickening, mesangial matrix increased. The expression of p-JNK and JNK in kidney increased significantly (all P <0.01), while the expression of nephrin decreased significantly (P <0.01). The levels of BUN, SCR, UAER and MDA in AA group were significantly lower than those in DM group (all P <0.05), and the SOD activity was significantly increased (P <0.05). The ultrastructure of podocytes was significantly improved. The expressions of p-JNK, (All P <0.05), and nephrin expression was significantly increased (P <0.05). Conclusion: AA may play a protective role in the kidney of diabetic rats by inhibiting the activity of JNK signal pathway and up-regulating the expression of nephrin in diabetic rats.