积雪草酸对糖尿病大鼠肾脏足细胞损伤的影响

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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。 Objective To investigate the effects of Asiatic acid on oxidative stress in kidney and expression of nephrin protein and protein in podocytes of diabetic rats. Methods Diabetic rats were induced by intraperitoneal injection of streptozotocin (65 mg · kg-1). Twenty-four successful rats were randomly divided into four groups. Six normal SD rats were used as normal control group. Asiatic acid low, medium and high dose groups were given asiatic acid 10,20,40 mg · kg-1 · d-1 orally, normal control group and diabetic model group were given the same amount of distilled water for 8 weeks. After intervention, blood urea nitrogen (BUN), serum creatinine (Scr), urinary albumin excretion rate (UAER), malondialdehyde (MDA) content and superoxide dismutase (SOD) The pathological changes of the kidneys were observed under the microscope and electron microscope. The expressions of nephrin protein and protein were detected by immunohistochemistry. Results Compared with the normal control group, the expression of BUN, Scr, UAER, renal MDA and desmin in diabetic model group were significantly increased, and the protein expression of SOD and nephrin in renal tissue was significantly decreased (P <0.01). The light microscope showed that the glomerular volume increased , Mesangial cells increased, electron microscopy showed foot to varying degrees of broadening, glomerular basement membrane thickening, mesangial matrix increased. Compared with diabetic model group, the expression of BUN, Scr, UAER, renal MDA and desmin in asiatic acid groups decreased (P <0.05 or P <0.01), and decreased with the increase of asiatic acid dose; nephrin protein expression increased (P <0.05 or P <0.01), with increasing doses of asiatic acid increased upward and the pathological changes of kidney under light and electron microscopy gradually improved. Conclusion Asiatic acid may play a protective role on the kidneys of diabetic rats by inhibiting the oxidative stress, raising the expression of nephrin protein and down-regulating the expression of neutrinosin in the kidney of diabetic rats.
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