2型糖尿病大鼠心肌组织MMP-2、MMP-9、TIMP-1的表达与胶原代谢的关系

目的 了解2型糖尿病（T2DM）大鼠模型心肌组织基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）及其组织抑制物1（TIMP-1）的mRNA表达变化、蛋白水平及组织定位，探讨MMPs／TIMPs在T2DM心肌病变发生发展中的作用。方法 Masson染色观察心肌胶原含量变化；RT-PCR方法观察心肌MMP-、MMP-9和TIMP-1mRNA表达；免疫组化方法测定MMP-2、MMP-9、TIMP-1的蛋白表达和组织定位。结果 T2DM大鼠心肌胶原纤维明显增多；MMP-2mRNA表达明显下调，蛋白水平下降；MMP-9、TIMP-1的mRNA表达均增加，MMP-9、TIMP-1的蛋白水平也升高，但MMP-9／TIMP-1的比值下降。结论 T2DM大鼠心肌组织胶原聚集，心肌纤维化。MMPs／TIMP-1比例失衡可能与T2DM心肌病变的发生有关。

The expression of MMP-2, MMP-9, TIMP-1 and the collagen metabolism in myocardial tissue of type 2 diabetic rats

Objective To study the expression of the MMP-2, MMP-9, TIMP-1 mRNA, their protein levels and localization in myocardial tissue of the rats with type 2 diabetes at different stages, and to elucidate the effects of the ratio of MMPs/TIMPs on diabetic myocardial damages. Methods Collagen content was observed by Masson staining. RT-PCR was used to observe the gene expression of MMP-2, MMP-9, TIMP-1 in diabetic rats myoeardium. The MMP-2, MMP-9, TIMP-1 proteins and their localization in rats myocardium were quantified by immunohistochemieal method. Results The amount of collagen fibre was increased in diabetic rats myoeardium. The expressions of MMP-2 mRNA and its protein were decreased in diabetic myoeardium. The expressions of MMP-9 and TIMP- 1 mRNA and their protein levels were increased, but the ratio of MMP-9 over TIMP-1 was decreased. Conclusions Collagen accumulation and cardiac fibrosis were observed in diabetic rats myoeardium. Imbalance of ratio of MMP-9 over TIMP-1 might be related to the pathogenesis of diabetic myocardial damages.