MMP-2和TIMP-2在肾间质纤维化大鼠模型中的表达和意义  

EXPRESSION OF MMP-2 AND TIMP-2 IN RENAL INTERSTITIAL FIBROSIS AFTER UNILATERAL URETERAL OBSTRUCTION IN RATS

作　　者：陆海英[1] 张悦[2] 周娟[2] 刘煜敏[2] 陆敏[2] 史美育[1] 

机构地区：[1]上海中医药大学护理学院,上海201203 [2]上海中医药大学科技实验中心

出　　处：《现代预防医学》2009年第12期2328-2331,共4页Modern Preventive Medicine

基　　金：国家自然基金项目(30500687);上海市高等学校科学发展基金项目(05CZ23)

摘　　要：[目的]观察基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶组织抑制因子-2(tissue inhibitor of matrix metalloproteinase-2,TIMP-2)在单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠模型中的动态表达,探讨MMP-2/TIMP-2在肾小管间质纤维化中的作用机制。[方法]54只SD大鼠随机分为正常组、假手术组和单侧输尿管梗阻模型组(UUO),分别于术后3d、7d、14d、21d处死,采用westernblot法检测肾组织MMP-2、TIMP-2蛋白表达水平;明胶酶谱法检测肾组织MMP-2的酶活性;HE染色光镜观察肾纤维化;电镜观察细胞外基质的变化。[结果]与假手术组相比,模型组肾组织MMP-2蛋白表达(F=125.558,P﹤0.01)、TIMP-2的蛋白表达(F=9.833,P﹤0.05)均于术后d3即出现增高并随梗阻时间延长递增。[结论]在大鼠UUO肾纤维化形成过程中,MMP-2的蛋白表达在肾损伤早期即明显增加,并随纤维化程度加重而逐步升高,从而促进肾纤维化的发生。而TIMP-2的高表达可能是加重肾间质损害的因素之一。[Objective] To observe the expression of matrix metalloproteinase：2 （MMP-2） and tissue inhibitor of matrix metalloproteinase-2 （TIMP-2） in unilateral ureteral obstruction （UUO） rats, and to explore its pathogenic role in renal tubule-interstitium fibrosis. [ Methods] 54 male SD rats were randomly divided into normal group, placebo group and left ureteral ligation group （UUO）, and they were executed at the time of 3, 7, 14 or 21 days （n=6 at each time point）. The protein expression level of MMP-2 and TIMP-2 in renal tissue was detected by Western blot method. Zymography were performed to detect the enzyme activity of MMP-2 in renal tissue. Renal fibrosis was detected by HE dying light microscope, and the change of extracellular matrix were observed by electron microscope. [ Results] When compared with SOR, the protein expression of MMP-2 （F = 125.558, P 〈 0.01 ） and TIMP-2 （F = 9.833, P 〈0.05） began to increase on the third day after UUO, and the protein level of them appeared to increase with the time. [Conclusion] In the process of the renal interstitial fibrosis in UUO rats, expression of MMP-2 was elevated from the early stage and positively associated with fibrosis stage, and then promoted the renal fibrosis. The higher protein expression of TIMP-2 might be one of reasons for inducing the renal interstitial fibrosis.

关 键 词：MMP-2 TIMP-2 肾间质纤维化 

分 类 号：R692[医药卫生—泌尿科学]