硫化氢通过调控Bcl-2/Caspase-3的表达减轻糖尿病大鼠心肌细胞凋亡和纤维化  

Hydrogen sulfide alleviates myocardial fibrosis and apoptosis in diabetic rats via regulating the expressions of Bcl-2 and Caspase-3

作　　者：刘茂军[1] 梁彪[1] 李子宁[1] 江振涛[1] 吴志雄[1] 褚春 杨军[1] LIU Mao-Jun;LIANG Biao;LI Zi-Ning(Department of Geriatrics,the First Affiliated Hospital of South China University Hengyang 421001,Hunan.China)

机构地区：[1]南华大学附属第一医院老年医学科,湖南衡阳421001 [2]南华大学附属第二医院药剂科

出　　处：《中国老年学杂志》2018年第22期5506-5509,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.81270181;81202830)

摘　　要：目的观察气体信号分子硫化氢(H_2S)通过调控Bcl-2/Caspase-3的表达对糖尿病大鼠心肌细胞凋亡和纤维化的影响。方法 50只成年雄性SD大鼠被随机分成5组(每组10只):正常对照组(Control组)、糖尿病组(模型组)、低浓度保护组(c1组)、高浓度保护组(c2组)、H_2S对照组(H_2S组)。通过腹腔注射链脲佐菌素(STZ)(40 mg/kg)的方法建成糖尿病大鼠实验模型;Control组每天通过腹腔注射同等剂量的生理盐水;硫氢化钠(NaHS)作为H_2S的供体,c1组每天注射30μmol/kg的Na HS溶液,c2组与H_2S组每天注射100μmol/kg的Na HS溶液。建模8 w后处死大鼠,免疫组化法检测心肌Ⅰ型胶原蛋白和Ⅲ型胶原蛋白的表达;通过Masson染色的方法观察心肌组织病理学发生的变化;用TUNEL染色的方法观察各组大鼠心肌细胞凋亡;Western印迹检测大鼠心肌组织Bcl-2和Caspase-3蛋白的表达水平。结果与Control组相比,模型组大鼠心肌细胞排列紊乱,存在明显胶原沉积和心肌纤维化,心肌组织中凋亡细胞数量明显增加,心肌组织中Caspase-3蛋白表达明显升高(P<0. 01),Bcl-2蛋白表达水平明显降低(P<0. 01);与模型组相比,c1和c2组大鼠心肌纤维有所改善,凋亡细胞数量明显减少,c1组和c2组Caspase-3蛋白明显降低(P<0. 05);c1组和c2组Bcl-2蛋白明显升高(P<0. 01)。结论 H_2S可改善糖尿病大鼠心肌纤维化,其机制可能与调控凋亡相关蛋白Bcl-2和Caspase-3的表达并减轻细胞凋亡有关。Objective To explore the effects of hydrogen sulfide（H2S） on myocardial fibrosis and apoptosis via regulating the expressions of Bcl-2 and Caspase-3.Methods 50 male SD rats were randomly divided into normal（control）,streptozotocin（STZ）,c1（diabetes mellitus treated with intraperitoneal infusions of Na HS 30 μmol/kg daily）,c2（ diabetes mellitus treated with daily intraperitoneal infusions of Na HS 100 μmol/kg）,H2S（normal rats treated with H2S）groups（n = 10）.Diabetic model was established by intraperitoneal injection of STZ,40 mg/kg.8 weeks later,Masson staining was used to detect the pathomorphologycal changes of myocardial fibers. Apoptosis of myocardialcell was analyzed by TUNEL assay.Results Compared with those of control group,the arrangement of myocardial cells was remarkable disordered,collagen deposion and myocardial fibrosis were found in STZ group,TUNEL-positive cardiomyocytes were dramatically raised in STZ group,the expression of Bcl-2 was significantly increased in STZ group（P〈0.01）,the expression of Caspase-3 was markedly decreased in STZ group（P〈0.01）. While all these changes were significantly reversed after treated with H2S in c1 and c2 groups.Conclusions H2S could improve myocardial fibrosis in diabetic rats which might be related to regulating the expressions of Bcl-2 and Caspase-3 and reducing apoptosis.

关 键 词：硫化氢 糖尿病心肌纤维化 细胞凋亡 BCL-2 CASPASE-3 

分 类 号：R587.1[医药卫生—内分泌]