清热益气通络方治疗DN大鼠蛋白尿机理研究

目的 研究清热益气通络方治疗糖尿病肾病（DN）大鼠蛋白尿的机制.方法 将60只SD大鼠随机分10只为正常组,50只为糖尿病肾病造模组（采用单侧肾切除腹腔注射链脲佐菌素的方法建立大鼠DN模型）.将造模成功的大鼠再分为模型组、中药组和厄贝沙坦组,治疗12周.检测肾/体质量指数（BW/KW）、24h尿微量白蛋白（umAlb）、24 h尿蛋白量（uPro）；酶联免疫吸附法（ELISA）检测10％肾组织匀浆超氧歧化酶（SOD）、过氧化氢酶（CAT）、还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）含量；免疫荧光双标法观察肾小球P钙黏蛋白（P-cadherin）、成纤维细胞特异蛋白1（FSP1）的表达免疫荧光标记肾胚胎瘤抑制基因（WT1）并计数.结果 模型组大鼠BW/KW、24 h umAlb、24h uPro、肾组织匀浆MDA、及FSP1显著增高（P＜0.01或P＜0.05）,SOD、CAT、GSH、GSH-Px及P-cadherin显著降低（P＜0.01或P＜0.05）,模型组大鼠肾小球WT1阳性细胞密度显著降低（P＜0.01）；清热益气通络方能显著降低DN大鼠BW/KW、umAlb、uPro、MDA水平及FSP1表达（P＜0.01或P＜0.05）,提高SOD、CAT活性、GSH含量及P-cadherin表达（P＜0.01或P＜0.05）.结论 减轻DN大鼠肾组织氧化应激及拮抗足细胞P-cadherin、FSP1异常表达是清热益气通络方药治疗DN蛋白尿的部分作用机制.

Qingreyiqitongluo Decoction on Proteinuria in Diabetic Nephropathy Rats

Objective： To investigate the mechanism of Qingreyiqitongluo Decoction （QD） in treating the diabetic nephropathy. Methods： 60 Sprague-Dawleg rats were divided into normal control group （N） and diabetic nephropathy model group prepared by intraperitoneal injection with STZ after unilateral nephrectomy. Then the model rats were assigned into model control group （M）,Irbesartan treatment group （I） and QD treatment group （Q）. After 12 weeks of treatment, 24-hour urine microalbumin （umAlb）, 24-hour urinary protein （uPro）, the con- tents of superoxide dismutase （SOD）, catalase （CAT）, reduced glutathione （GSH）, lutathione peroxidase （GSH - Px）, and malondialdehyde （MDA） in renal tissue were examined ; fibroblast-fpecific protein 1 （FSP1）, P-cadherin, wilms tumor 1 （WT1） in glomerulus were observed by means of immunofluorescence double labeling. Results： Compared with N group,the levels of 24 h umAlb,24 h uPro,MDA and the expressions of FSP1 were markly in- creased （P〈 0.01 or P〈 0.05 ）;the contents of SOD, CAT, GSH-Px and the expressions of P-cadherin were signifi- cantly decreased （P〈0.01 or P〈0.05）. QD decreased the levels of umAlb,uPro,MDA, the expressions of FSP1, and increased the contents of SOD,CAT,GSH ,the expressions of P-eadherin markbly （P〈 0.01 or 0.05）. Con- clusions： QD has a protective effect on the experimental diabectic nephrepathy rats. The mechanism may be re- lated to improving the body＇s antioxidant ability and inhibiting podocyte epithelial-mesenchymal transition（EMT） by means of improving the expression of P-cadherin as well as decreasing the expression of FSP1.