硫化氢通过抑制STAT1通路改善高甲状腺素导致的大鼠心肌纤维化  

Hydrogen sulfide inhibits myocardial fibrosis induced by thyroxine in rats by inhibiting STAT1 pathway

作　　者：谭文婷[1] 李琳[1] 唐芬[1] 刘盛权 龙俊蓉 刘茂军[1] 梁彪[1] 李子宁[1] 褚春[2] 杨军[1] 

机构地区：[1]南华大学附属第一院心血管内科,湖南衡阳421001 [2]南华大学附属第二医院药剂科,湖南衡阳421001

出　　处：《临床心血管病杂志》2017年第8期790-793,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金项目(No:81270181;81202830)

摘　　要：目的:观察硫化氢对高甲状腺素导致的大鼠心肌纤维化及基质金属蛋白酶14(MMP14)、MMP16和转录激活因子1(STAT1)蛋白表达的影响。方法:取SD雄性大鼠随机分为4组:对照组(C组),甲亢性心肌组(L-Thy组),硫化氢+甲亢性心肌组(H2S+L-Thy组),硫化氢干预组(H2S组)。经腹腔注射左旋甲状腺激素(Left thyroid hormone,L-Thy)建立甲状腺功能亢进大鼠模型,C组相同步骤每日给予等量0.9%氯化钠,H2S+L-Thy组和H2S组经腹腔注射硫氢化钠溶液;Masson染色观察心肌纤维化及计算心肌胶原容积分数(Collagen volume fraction,CVF);Western blotting检测MMP14、MMP16和STAT1蛋白的表达。结果:与C组相比,LThy组心肌细胞紊乱,心肌纤维沉积明显增多、CVF增高(P<0.05),心肌MMP14、MMP16以及STAT1蛋白的表达均上调(P<0.05);而与L-Thy组相比,H2S+L-Thy组大鼠心肌组织纤维沉积明显减少、CVF下降(P<0.05),MMP14、MMP16以及STAT1的表达均有所下调(P<0.05)。结论:硫化氢可能通过STAT1通路下调MMP14和MMP16表达水平,并改善高甲状腺素导致的大鼠心肌纤维化。Objective：To observe the effect of hydrogen sulfide on myocardial fibrosis and matrix metalloproteinase 14（MMP14）,matrix metalloproteinase 16（MMP16）and activating transcription factor 1（STAT1）expression in hyperthyroid cardiomyopathy rat.Method：SD male rats were randomly divided into 4groups：control group（C）,hyperthyroid group（L-Thy）,hydrogen sulfide＋hyperthyroid group（H2S＋L-Thy）,hydrogen sulfide intervention group（H2S）.Masson staining was used to observe myocardial fibrosis and calculate myocardial collagen volume fraction;the expression of MMP16,MMP14 and STAT1protein were detected by western blotting.Result：compared with C group,the myocardial cell disorder in rats with hyperthyroid cardiomyopathy.Myocardial fiber deposition increased,CVF increased（P0.05）,expression of myocardial MMP14,MMP16 and STAT1protein were increased（P0.05）in L-Thy group;Compared with L-Thy group,H2S＋L-Thy group myocardial cell disorder improved,CVF decreased（P0.05）,MMP14,MMP16 and STAT1expression decreased（P0.05）.Conclusion：Hydrogen sulfide may down regulate the expression of MMP14 and MMP16through the STAT1 pathway,and improve the myocardial fibrosis induced by thyroxine in rats.

关 键 词：硫化氢 甲状腺功能亢进性心肌病 基质金属蛋白酶 转录激活因子1 

分 类 号：R542.2[医药卫生—心血管疾病]