益肾胶囊对糖尿病肾病大鼠肾组织SOCS3、TGF-β1、MCP-1表达的影响

摘要

目的:观察益肾胶囊对糖尿病肾病(DN)大鼠肾组织细胞因子信号抑制因子-3(SOCS3)、TGF-β1、MCP-1表达水平的影响.方法:40只健康雄性Wistar大鼠随机分为正常对照组、DN模型组(模型组)、益肾胶囊组、氯沙坦组,每组各10只.单侧肾切除加链脲佐菌素(STZ)腹腔注射建立DN大鼠模型,益肾胶囊组每只灌胃益肾胶囊(625 mg·kg-1·d-1),氯沙坦组每只灌胃氯沙坦钾片(30 mg·kg-1·d-1),正常对照组及模型组每日给予等量蒸馏水.测定各组大鼠体重、24 h尿蛋白定量、尿微量白蛋白、血肌酐(Scr)、尿素氮(BUN),并计算内生肌酐清除率(Ccr);取肾组织行病理组织学观察,免疫荧光法检测肾组织中SOCS3、TGF-β1、MCP-1表达水平.结果:实验12周末,模型组大鼠24 h尿蛋白定量、尿微量白蛋白、Scr、BUN均高于正常对照组(P<0.05),肾组织中SOCS3、TGF-β1、MCP-1表达水平高于正常对照组(P<0.05);治疗组大鼠24 h尿蛋白定量、尿微量白蛋白、Scr、BUN均低于模型组(P<0.05),Ccr较模型组升高(P<0.05),而低于正常对照组(P<0.05),肾组织中SOCS3表达水平明显高于模型组(P<0.05),而TGF-β1、MCP-1的表达受到抑制(P<0.05);两治疗组间比较差异无统计学意义.结论:益肾胶囊可能通过上调SOCS3在肾组织的表达,抑制了TGF-β1、MCP-1的表达,从而减轻了DN大鼠肾小球硬化和间质纤维化的程度,延缓DN的进展.%Objective:To investigate the effect of YiShen capsule on the expression of SOCS3 ,TGF - β1 and MCP - 1 in renal tissue of rats with diabetic nephropathy. Methods:40 Wistar rats were divided randomly into four groups:control, model, Yishen capsule treatment and losartan treatment, 10 rats each group. The rat models were induced by right nephrectony and peritoneal injection of low -dosage streptozotocin,the rats were treated with yishen capsule ( 625 mg · kg-1 · d-1 ) / Losartan potassium ( 30 mg ·kg - 1 · d - 1 ) by a stomach tube in treatment group, and same amount of water was fed in control and model group. Body weight, urinary protein/24 h, microalbuminuria, serum creatinine ( Scr ), blood urea nitrogen ( BUN ), and endogenous creatinine clearance rate ( Ccr )were measured,and optics microscope was adopted to observe the renal pathological changes. Expression levels of SOCS3,TGF - β1 and MCP - 1 in renal tissue of rats were detected by immunofluorescence microscope. Results:In 12w, urinary protein/24 h, microal buminuria, Scr, BUN in model group were higher significantly compared with contol group ( respectively, P ＜ 0.05 ). The expression of SOCS3 ,TGF - β1 and MCP - 1 of renal tissue in model group were higher significantly compared with control group ( respectively,P ＜0.05 ). After treatment of Yishen capsule / Losartan potassium, urinary protein/24 h, microalbuminuria, Scr, BUN were reduced ( respectively ,P ＜ 0.05 ). Ccr were higher compared with model group ( respectively,P ＜ 0.05 ), but lower than control group ( respectively, P ＜ 0.05 ). The expression of SOCS3 of renal tissue in treatment group were higher significantly ( respectively, P ＜ 0.05 ). The expression of TGF - β1 and MCP - 1 of renal tissue in treatment group were lower ( respectively,P ＜ 0.05 ). Two treatment groups weot statistically significant. Conclusion:After treatment of Yishen capsule / Losartan potassium, the expression of SOCS3 of renal tissue were higher significantly,the expression of TGF - β1 and MCP - 1 were decreased. To reduced glomerular sclerosis and interstitial fibrosis, delay the progress of the diabetic nephropathy effectively.