硫化氢对糖尿病大鼠心肌纤维化和MMP-2/TIMP-2表达的影响  

Effects of hydrogen sulfide on myocardial fibrosis and the expression of MMP-2/TIMP-2 in diabetic rats

作　　者：李芳[1] 吴志雄[1] 罗健[1] 肖婷[1] 曾欧[1] 张晶晶[1] 杨军[1] 

机构地区：[1]南华大学附属第一医院心血管内科,湖南衡阳421001

出　　处：《重庆医学》2015年第34期4765-4767,共3页Chongqing medicine

基　　金：国家自然科学基金资助项目(81270181);国家自然科学基金资助项目(81202830)

摘　　要：目的观察硫化氢(H2S)对糖尿病大鼠心肌纤维化和基质金属蛋白酶-2(MMP-2)/基质金属蛋白酶抑制剂-2(TIMP-2)表达的影响。方法将40只SD成年雄性大鼠随机分为4组(每组10只):正常对照组(Control组)、糖尿病模型组(STZ组)、硫化氢处理糖尿病组(STZ+H2S组)、硫化氢处理正常组(H2S组)。以链脲佐菌素(STZ)腹腔注射诱导糖尿病大鼠模型;苏木素-伊红(HE)染色观察心肌纤维病理形态学变化;Western blotting检测大鼠心肌组织Ⅲ型胶原、MMP-2和TIMP-2的表达水平。结果与对照组相比,STZ组心肌细胞排列紊乱,Ⅲ型胶原及TIMP-2表达水平显著升高(P<0.05),而MMP-2表达明显降低(P<0.05),MMP-2/TIMP-2的比值下降;与STZ组相比,STZ+H2S组TIMP-2及Ⅲ型胶原表达明显下调(P<0.05),MMP-2表达明显升高(P<0.05),MMP-2/TIMP-2的比值明显增加。结论硫化氢可改善糖尿病大鼠的心肌纤维化程度,其机制可能与其上调MMP-2表达、下调TIMP-2表达有关。Objective To explore the effects of hydrogen sulfide（H2S） on the expression of MMP-2, TIMP-2 and myocardial fibrosis in diabetic rats. Methods Totally 40 SD rats were randomly divided into four groups（n=10） ：control group,diabetes group （STZ group） , hydrogen sulfide treatment group （STZ＋H2S group） and normal rats treating with hydrogen sulfide group（H2S group）. Diabetes was induced in rats by intraperitoneal injection of streptozotocin（STZ）. The pathological morphological changes in myocardial fiber were analyzed by HE staining. The expression levels of matrix metalloproteinase 2 （MMP-2）, tissue inhibitor of metalloproteinase 2（TIMP-2 ） and collagen Ⅲ were analyzed by Western blotting. Results Compared with control group, collagen accumulation and cardiac fibrosis were observed in diabetic ratsr myocardium, the expression levels of collagen Ⅲ and TIMP-2 sig- nificantly increased（P〈0.05）, while the level of MMP-2 decreased（P〈0.05）,and the ratio of MMP-2 over TIMP-2 decreased in STZ group. Compared with STZ group, TIMP-2 and collagen Ⅲ significantly decreased in STZ＋H2S group（P〈0. 05）, the expression of MMP-2 significantly increased （P〈0.05） ,the ratio of MMP-2/TIMP-2 significantly increased. Conclusion H2S could at- tenuate myocardial fibrosis in diabetic rats, and its mechanism might be related with down-regulation of TIMP-2 and up-regulation of MMP-2.

关 键 词：硫化氢 基质金属蛋白酶2 糖尿病 心肌纤维化 

分 类 号：R587.2[医药卫生—内分泌]