积雪草酸对糖尿病大鼠肾脏足细胞损伤的影响  

Effects of asiatic acid on renal podocyte injury in diabetic rats

作　　者：陈宇宁[1] 吴晨光[2] 钱珂[1] 丁怡[1] 

机构地区：[1]苏州大学附属第三医院干部病房3,江苏常州213000 [2]江苏大学附属人民医院内分泌科,江苏镇江212002

出　　处：《中国新药与临床杂志》2014年第10期741-746,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：江苏省卫生厅面上项目(H200830)

摘　　要：目的探讨积雪草酸对糖尿病大鼠肾脏氧化应激及足细胞nephrin蛋白和结蛋白表达的影响。方法腹腔注射链脲佐菌素(65 mg·kg-1)诱导大鼠糖尿病模型,造模成功大鼠24只随机分为四组,并以6只正常SD大鼠作为正常对照组。积雪草酸低、中、高剂量组予积雪草酸10、20、40 mg·kg-1·d-1灌胃,正常对照组与糖尿病模型组予等量蒸馏水灌胃,连续8周。干预结束后测定各组血尿素氮(BUN)、血肌酐(Scr)、尿白蛋白排泄率(UAER),肾皮质丙二醛(MDA)含量及超氧化物岐化酶(SOD)活力;光镜、电镜下观察各组肾脏病理形态学改变;免疫组化法检测各组肾脏足细胞nephrin蛋白和结蛋白表达变化。结果与正常对照组比较,糖尿病模型组BUN、Scr、UAER、肾脏MDA和结蛋白表达均明显升高,肾脏SOD、nephrin蛋白表达明显降低(P<0.01);光镜示肾小球体积增大、系膜细胞数量增多,电镜示足突不同程度增宽、肾小球基底膜增厚、系膜基质增多。与糖尿病模型组比较,积雪草酸各剂量组BUN、Scr、UAER、肾脏MDA和结蛋白表达均下降(P<0.05或P<0.01),随着积雪草酸剂量增加呈下降趋势;肾脏SOD、nephrin蛋白表达均上升(P<0.05或P<0.01),随着积雪草酸剂量增加呈上升趋势且肾脏光镜、电镜下病理形态学异常逐渐改善。结论积雪草酸可能通过抑制糖尿病大鼠肾脏氧化应激,上调足细胞nephrin蛋白表达、下调结蛋白表达,发挥对糖尿病大鼠肾脏的保护作用。AIM To explore the effects of asiatic acid on renal oxidative stress and podocyte injury in diabetes mellitus rats. METHODS The diabetic rats model was induced by intraperitoneal injection of streptozotocin（ 65 mg·kg-1）. Twenty- four rats were induced successfully and were randomly divided into four groups. In addition, six normal SD rats were used as control group. Groups of low, middle and high dose asiaticacid were gavaged asiatic acid as 10, 20, 40 mg·kg-1·d-1. The control group and diabetic model group were gavaged distilled water for 8 weeks. After intervention, blood urea nitrogen（ BUN）, serum creatinine（ Scr）,urinary albumin excrection rate（ UAER）, levels of malondiadehyde（ MDA） and activities of superoxide dismutase（ SOD） in renal cortex were detected. Histomorphologic changes of kidneys were observed by optics microscope and electron microscope. Expressions of nephrin and desmin protein in podocytes were evaluated by immunohistochemistry. RESULES Compared with the control group, BUN, Scr, UAER, MDA and desmin protein in renal cortex of diabetic model group were significantly increased（P〈0.01）, while SOD and nephrin protein were significantly decreased（ P〈0.01）. In the diabetic model group, the glomerular hypertrophy,mesangial cell proliferation was observed by optics microscope. By electron microscope, the foot process width were increased, the glomerulus basement membranes were thickened, and the mesenterium mass were increased. Compared with the diabetic model group, BUN, Scr, UAER, MDA and desmin were significantly decreased in each asiatic acid group（ P〈0.05 or P〈0.01）. With the dose of asiatic acid increasing, all of above indexes had the trends of decreasing. SOD and nephrin protein were significantly increased in each asiatic acid group（ P〈0.05 or P〈0.01）, and had the trends of rising with the dose of asiatic acid increasing. In addition, the abnormal histomorphologic changes had gradually improvement in each asiatic acid group.CONCLUSION Asi

关 键 词：糖尿病 肾病 积雪草酸 足细胞 结蛋白 NEPHRIN 

分 类 号：R587[医药卫生—内分泌]