中药对肾小球硬化大鼠MMP-9、TIMP-1及TGF-β_1mRNA表达的影响

Effect of stasis in collaterals of renal Chinese medicine compound prescription on the renal expressions of MMP-9,TIMP-1 and TGF-β_1mRNA in glomerulosclerosis rats

目的探讨肾络癥积中药复方对肾小球硬化大鼠细胞外基质降解调控系统MMP-9、TIMP-1及TGF-β1mRNA的影响。方法采用切除单侧肾脏同时尾静脉注射阿霉素的方法 ,建立肾小球硬化大鼠模型,检测各组大鼠24小时尿蛋白定量,ELISA法检测基质金属蛋白酶(MMP-9)、基质金属蛋白酶抑制物(TIMP-1)的表达,计算MMP-9/TIMP-1比值,荧光定量PCR法检测细胞TGF-β1mRNA。结果各中药组大鼠24小时尿蛋白均小于模型组(P<0.05),与模型组比较,各中药组均能抑制TIMP-1的表达(P<0.05),上调MMP-9(P<0.05),提高MMP-9/TIMP-1的比值(P<0.05),并下调细胞中TGF-β1mRNA表达(P<0.05)。结论祛瘀化痰、散结消癥中药复方,可抑制TIMP-1,上调MMP-9,下调TGF-β1mRNA的表达,其机制可能是通过增强细胞外基质降解,对肾小球硬化大鼠肾功能产生保护作用。

Objective To investigate the effect of the Chinese medicine compound prescription on the MMP-9,TIMP-1 and TGF-β1mRNA in glomerulosclerosis（GS）rats.Methods GS rat model was established by unilateral nephrectomy and adriamycin injection,in which 24h urinary protein of rats were observed,the expressions of matrix metalloproteinase-1（MMP-1）,tissue inhibitor of metalloproteinase 1（TIMP-1）were detected by ElISA and the ratio of MMP-9/TIMP-1 was calculated,and the expression of transforming growth factor-β1mRNA（TGF-β1 mRNA）was detected by fluorescence quantitative PCR for each group of rats.Results The 24 hour urinary protein of all rats in the Chinese medicine groups was lower than the model group（P0.05）,the expression of TIMP-1（P0.05）was inhibited,MMP-9（P0.05）was increased,the ratio of MMP-9/TIMP-1（P0.05）was enhanced and the expression of TGF-β1 mRNA（P0.05）was inhibited.Conclusion The Chinese medicine compound prescription,which is able to remove blood stasis and reducing phlegm and disperse stagnated mass,is protective to GS rats,and whose mechanism might be related to increasing the degradation of ECM,decreasing the expression of TGF-β1 mRNA.