基质金属蛋白酶的表达和活性与2型糖尿病大鼠大血管病变的相关性研究

The Relationship between the Expression and Activity of MMP in Arterial Wall and Type 2 Diabetic Macroangiopathy

目的探讨基质金属蛋白酶(MMP-9、MMP-2)的表达和活性与2型糖尿病(T2DM)大鼠大血管病变的关系。方法高脂饲料加小剂量链脲佐菌素(Streptozotocin,STZ)建立T2DM大鼠模型,0、4、8和12周末取大鼠主动脉。免疫组化和RT-PCR分别检测MMP-9、MMP-2蛋白和mRNA表达;含明胶的SDS PAGE电泳检测MMP-9、MMP-2的活性;病理图像分析主动脉相对病变面积。结果T2DM组主动脉病变逐渐加重,各时间点主动脉壁MMP-9表达及活性随病程延长而增加,且MMP-2、MMP-9的表达与斑块面积占主动脉内膜总面积的百分比成正相关(r=0.801,P<0.05)。结论T2DM大血管病变形成过程中伴有MMP-9、MMP-2表达和活性的变化,MMP-9、MMP-2在T2DM大血管病变的发生与发展过程中起一定作用。

Objective To investigate the relationship between the expression and activities of matrix metalloproteinase（MMP-9,MMP-2） and type 2 diabetic macroangiopathy. Methods Type 2 diabetic rat model was established by high-fat diet and a low dose of STZ. The protein and mRNA expressions of MMP-9 and MMP-2 were measured by immunohistochemistry and RT-PCR respectively. The activities of MMP-9 and MMP- 2 were measured by SDS-PAGE zymography. The pathological changes of aortic wall were observed by HE and Sudan IV staining and analyzed by computer. Results The expression and activities of MMP-9 and MMP-2 in DM model rats were significantly increased during the development of macroangiopathy. Conclusion The changes of MMP-9 and MMP-2 expression and activities occur during the development of type 2 diabetic maeroangiopathy,which implies that MMPs may play an important role in the development and progression of type 2 diabetic macroangiopathy.