吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (02): 235-239.doi: 10.13481/j.1671-587x.20150206

• 基础研究 • 上一篇    下一篇

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

褚春1, 曾欧2, 罗健2, 李芳2, 肖婷2, 周松柏2, 杨军2   

  1. 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
  • 收稿日期:2014-08-07 出版日期:2015-03-28 发布日期:2015-04-04
  • 通讯作者: 杨军, 主任医师, 硕士研究生导师(Tel:0734-8578765, E-mail:yangjunincn@163.com) E-mail:yangjunincn@163.com
  • 作者简介:褚春(1977-), 女, 湖南省衡阳市人, 副主任药师, 在读医学硕士, 主要从事临床药理学方面的研究。
  • 基金资助:

    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)

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

CHU Chun1, ZENG Ou2, LUO Jian2, LI Fang2, XIAO Ting2, ZHOU Songbai2, YANG Jun2   

  1. 1. Department of Pharmacy, Second Affiliated Hospital, South China University, Hengyang 421001, China;
    2. Department of Cardiology, First Affiliated Hospital, South China University, Hengyang 421001, China
  • Received:2014-08-07 Online:2015-03-28 Published:2015-04-04

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100 μmol·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。

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

Abstract:

Objective To explore the effects of hydrogen sulfide (H2S) on the myocardial fibrosis and the expressions of membrane-type 1 matrixmetallo-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 H2S on the development of the myocardial fibrosis and its mechanism.Methods 52 rats were randomly divided into control group,DM group,DM+H2S group and H2S 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 H2S group(n=10) were administrated with 100 mg·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-2 proteins 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 type Ⅲ collagen,MT1-MMP and TIMP-2 proteins 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-2 proteins in the myocardium tissue of the rats in DM+H2S group were significantly decreased (P<0.05).Conclusion H2S 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.

Key words: hydrogen sulfide, membrane-type 1 matrixmetallo-proteinase, tissue inhibitor of metalloproteinase-2, diabetes mellitus, myocardial fibrosis

中图分类号: 

  • R587.1