积雪草酸对糖尿病大鼠肾脏c-Jun氨基末端激酶信号通路的影响  

The effect of asiatic acid on renal c-Jun N-terminal kinase signaling pathway in diabetic rats

作　　者：陈宇宁[1] 陈艳[1] 王丽[1] 徐志刚[1] 李文[1] 吴晨光[1] 

机构地区：[1]江苏大学附属人民医院内分泌科,江苏镇江212002

出　　处：《南京医科大学学报（自然科学版）》2011年第3期399-403,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省卫生厅面上项目(H200830);镇江市医学重点人才基金[镇卫字(2005)237号]

摘　　要：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。Objective：To explore the effect of asiatic acid（AA） on renal c-Jun N-terminal kinase（JNK） signaling pathway and podocyte in diabetic rats.Methods：Diabetic model was established by injection of streptozotocin.The diabetic rats were divided into two groups： diabetes mellitus group（DM group） and AA treated group（AA group）.The normal non-diabetic rats were served as the control group（NC group）.After eight weeks,the serum urea nitrogen（BUN）,serum creatinine（SCR）,the excretion of urinary albumin excretion rate（UAER）,the blood glucose,the activity of superoxide dismutase（SOD） and the level of malonaldehyde（MDA） in renal cortex were detected.The structure of podocytes was observed by electron microscope.The expressions of p-JNK and JNK protein in kidney tissue of rats were examined by Western blot.The expression of nephrin protein in podocyte was examined by immunohistochemistry.Results：Compared with NC group,in DM group,the levels of BUN,SCR,UAER and blood glucose were significantly elevated（all P 〈 0.01）;the level of MDA in renal cortex was significantly elevated（P 〈 0.05）;the activity of SOD was significantly reduced（P 〈 0.05）;the foot process width was increased,the glomerulus basement membrane was thickened,the mesenterium mass were increased;the expressions of p-JNK and JNK in kidney tissue were significantly increased（all P 〈 0.01）;the nephrin expression was significantly reduced（P 〈 0.01）.Compared with DM group,in AA group,the levels of BUN,SCR,UAER,and MDA in renal cortex were significantly reduced（all P 〈 0.05）;the activity of SOD was significantly increase（P 〈 0.05）;the abnormal structure of podocyte was obviously improved;the expressions of p-JNK and JNK were significantly reduced（all P 〈 0.05）;the nephrin expression was significantly increased（P 〈 0.05）.Conclusion： Asiatic acid may up-regulate the expression of nephrin in the podocyte of DM rats and inhibit the JNK signaling pathway activation showing the

关 键 词：糖尿病肾病 积雪草酸.c-Jun氨基末端激酶 NEPHRIN 

分 类 号：R587.1[医药卫生—内分泌]