硫化氢对糖尿病大鼠心肌组织中MT1-MMP和TIMP-2蛋白表达及心肌纤维化的影响及其机制  

Effects of hydrogen sulfide on expressions of MT1-MMP and TIMP-2 proteins and myocardial fibrosis in myocardium tissue of diabetic rats and their mechanisms

作　　者：褚春[1] 曾欧[2] 罗健[2] 李芳[2] 肖婷[2] 周松柏[2] 杨军[2] 

机构地区：[1]南华大学附属第二医院药剂科,湖南衡阳421001 [2]南华大学附属第一医院心血管内科,湖南衡阳421001

出　　处：《吉林大学学报（医学版）》2015年第2期235-239,I0002,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81202830);湖南省科技厅自然科学基金资助课题(11JJ2046)

摘　　要：目的:观察气体信号分子硫化氢(H2S)对糖尿病(DM)大鼠心肌纤维化和膜型基质金属蛋白酶1(MT1-MMP)和基质金属蛋白酶组织抑制因子2(TIMP-2)蛋白表达的影响,探讨其在心肌纤维化发生发展中的作用和相关机制。方法:52只SD大鼠随机分为对照组(Control组)、糖尿病模型组(DM组)、硫化氢干预糖尿病组(DM+H2S组)和硫化氢干预正常组(H2S组),每组13只。以链脲佐菌素(STZ)腹腔注射建立DM大鼠模型,模型构建成功后对照组(n=12)和DM组(n=9)大鼠每天腹腔注射生理盐水;DM+H2S组(n=9)和H2S组(n=10)大鼠每天腹腔注射100μmol·kg-1硫氢化钠溶液,8周后处死大鼠取左心室心肌组织,VG染色观察大鼠心肌组织形态学;Western blotting法检测大鼠心肌组织中Ⅲ型胶原、MT1-MMP和TIMP-2蛋白的表达水平。结果:与对照组比较,DM组大鼠心肌细胞排列紊乱,胶原沉积增多,心肌存在明显心肌纤维化,心肌组织中Ⅲ型胶原蛋白、MT1-MMP和TIMP-2蛋白表达水平明显升高(P<0.05);与DM组比较,DM+H2S组大鼠心肌纤维化有所改善,心肌组织中Ⅲ型胶原蛋白、MT1-MMP和TIMP-2蛋白表达水平明显降低(P<0.05)。结论:H2S可改善DM大鼠的心肌纤维化并下调Ⅲ型胶原蛋白的表达,其机制可能与其下调MT1-MMP蛋白表达以及改善MT1-MMP/TIMP-2蛋白失衡有关。Objective To explore the effects of hydrogen sulfide（H2S）on the myocardial fibrosis and the expressions of membrane-type 1matrixmetallo-proteinase（MT1-MMP）and tissue inhibitor of metalloproteinase-2（TIMP-2）in the myocardium tissue of the rats with diabetes mellitus（DM）,and to clarify the effect of H2 S on the development of the myocardial fibrosis and its mechanism.Methods 52 rats were randomly divided into control group,DM group,DM＋ H2 S group and H2 S group（n=13）.The rat models were induced by intraperitoneal injection of streptozotocin（STZ）.The rats in control group（n=12）and DM group（n=9）were injected with saline after modeling and the rats in DM＋H2S group（n=9）and H2 S group（n=10）were administrated with100mg·kg-1 NaHS.After 8 weeks,the pathomorphology of myocardium tissue of the rats in various groups were analyzed by VG staining;the expression levels of type Ⅲ collagen,MT1-MMP and TIMP-2proteins in the myocardium tissue of the rats were analyzed by Western blotting method.Results Compared with control group,disorgnised array in the myocardial cells,collagen deposition and myocardial fibrosis of the rats were found in DM group;the expression levels of typeⅢ collagen,MT1-MMP and TIMP-2proteins in myocardium tissue of the rats were significantly increased（P〈0.05）.Compared with DM group,the myocardial fibrosis was improved of the rats in DM＋H2S group,and the expression levels of type Ⅲ collagen,MT1-MMP and TIMP-2proteins in the myocardium tissue of the rats in DM＋H2S group were significantly decreased（P〈0.05）.Conclusion H2 S could improve the myocardial fibrosis and decrease the expression of type Ⅲ collage protein in diabetic rats and its mechanism may be related to the down-regulation of MT1-MMP and the improvement of the imbalance of MT1-MMP/TIMP-2.

关 键 词：硫化氢 膜型基质金属蛋白酶1 基质金属蛋白酶抑制剂2 糖尿病 心肌纤维化 

分 类 号：R587.1[医药卫生—内分泌]