金属蛋白酶-2和金属蛋白酶组织抑制物-1与糖尿病肾病关系的实验研究

目的　观察链脲佐菌素 (STZ)实验性糖尿病大鼠肾脏基质金属蛋白酶 2 (MMP 2 )及金属蛋白酶组织抑制物 1(TIMP 1)蛋白的表达及功能、形态学改变 ,探讨MMP 2、TIMP 1在糖尿病肾病(DN)发生机制中的意义。　方法　 2 0只雄性Wistar大鼠随机分为糖尿病组和正常对照组 ,分别于第1、2、4、6、8周测定尿白蛋白排泄率 (UAER) ,第 9周用Western印迹方法检测MMP 2、TIMP 1蛋白表达水平 ,电镜观察肾小球基底膜厚度 (GBMT)。　结果　糖尿病组较正常组TIMP 1蛋白表达明显增加 ,MMP 2蛋白表达显著降低 (P <0 .0 1)。 4、6、8周UAER显著增加 ,GBMT明显增厚 (P <0 .0 1)。电镜发现糖尿病组肾小球基底膜弥慢性增厚 ,局部有系膜细胞插入和双轨征。　结论　持续高血糖可使大鼠肾脏MMP 2下降 ,TIMP 1增加。导致肾小球基底膜增厚 ,UAER增加。MMP 2、TIMP 1失衡可能对糖尿病肾病功能和形态学改变有重要意义。

An experimental study on the relationship of MMP-2 and TIMP-1 with diabetic nephropathy

Objective To observe the expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and changes in the correlative function and morphology in streptozotozin-induced experimental diabetes mellitus rats. To explore the roles of MMP-2 and TIMP-1 in the pathogenesis of diabetic nephropathy. Methods 20 rats were randomly divided into two groups: normal control and diabetes groups. Urinary albumin excretion rate (UAER) were assayed at week 1, 2, 4, 6 and 8. The protein expression of MMP-2 and TIMP-1 in renal cortex were determined by Western- blot and the glomerular basement membrane thickness (GBMT) were measured by image analysis at week 9. The ultrastructure of glomerular basement membrane was observed by electron microscope. Results Compared with normal control group, the expression of MMP-2 protein decreased significantly (P<0.01) and TIMP-1, UAER and GBMT were markedly increased in diabetic rats (P<0.01), respectively. Conclusions Long lasted hyperglycemia can lead to the increase of TIMP-1 and the decrease of MMP-2. The unbalance between MMP-2 and TIMP-1 may play an important role in renal dysfunction and morphological changes of diabetic nephropathy.