肾复汤对糖尿病大鼠肾组织MMP-9、TIMP-1表达的影响

Effect of Shenfutang on expression of MMP-9 and TIMP-1 in kidney tissues of diabetes mellitus rats

目的观察肾复汤对糖尿病(DM)大鼠肾脏病变的保护作用及其机制。方法建立STZ诱导的糖尿病SD大鼠模型,随机分成4组:正常对照组、DM模型组、肾复汤治疗组及厄贝沙坦治疗组。各组大鼠采用相应的干预措施处理12周。常规方法检测各组大鼠肾重/体重、血糖、尿素氮、血肌酐、尿白蛋白排泄率(UAER),免疫组化法检测肾组织MMP-9、TIMP-1表达,透射电镜观察肾脏超微结构。结果 DM模型组大鼠肾组织MMP-9的表达较正常对照组明显下调(P<0.01),经肾复汤治疗后肾组织MMP-9表达明显上调(P<0.01),但仍低于正常对照组(P<0.01);DM模型组大鼠肾组织TIMP-1的表达较正常对照组明显上调(P<0.01),经肾复汤治疗后肾组织TIMP-1表达明显下调(P<0.01),但仍高于正常对照组(P<0.01)。血糖、UAER、尿素氮、血肌酐、肾重/体重等肾复汤治疗组指标值较DM模型组有所下降(P<0.01)。结论 MMP-9、TIMP-l的表达变化与肾小球细胞外基质(ECM)降解减少相关,可能促进了糖尿病肾病的发生,肾复汤可能通过干预这种表达变化减缓糖尿痛肾病的发生和发展。

ObjectiveTo investigate the protective effects of Shenfutang on renal lesion in diabetic rats.MethodsThe diabetic SD rats were induced by STZ,and divided into four groups（normal control group,diabetic control group,Shenfutang group and irbesartan group）.Rats in each group were treated for 12 weeks by above intervention methods respectively.The relative kidney weight,blood sugar,urea nitrogen,serum creatinine,and urinary albumin excretion rate（UAER） were detected by ordinary methods,MMP-9 and TIMP-1 in renal tissues were detected by immunohistochemical techniques,and ultrastructure of kidney was observed by transmission electron microscope.ResultsCompared with normal control group,the expression of MMP-9 was decreased in diabetic control group（P〈0.05）.The expression of MMP-9 in Shenfutang group was higher than that in diabetic control group（P〈0.05）,but was still lower than that in normal control group（P〈0.05）.Compared with normal control group,the expression of TIMP-1 was increased in diabetic control group（P〈0.05）.The expression of TIMP1 in Shenfutang group was lower than that in diabetic control group（P〈0.05）,but was still higher than that in normal control group（P〈0.05）.The ultrastructure of kidney was noticeably changed,and the blood sugar,UAER,urea nitrogen,serum creatinine,and relative kidney weight were significantly increased in diabetic rats,while the above indexes were significantly lower in Shenfutang group than in diabetic control group（P〈0.05）.Conclusion The change of the expressions of MMP-9 and TIMP-1 is related to decreased extracellular matrix degradation,which may promote the occurrence and progress of diabetic nephropathy.Shenfutang may attenuate the occurrence and progress of diabetic nephropathy through interfering with this change.