硫化氢通过调控JNK通路改善H型高血压大鼠心肌纤维化  

Hydrogen sulfide ameliorating myocardial fibrosis in H-type hypertensive rats through regulating JNK pathway

作　　者：李亚灵 刘茂军[1] 郑霞 易嘉莉 宋熊 刘达 王森 杨军[1] LI Ya-Ling;LIU Mao-Jun;ZHENG Xia(Department of Cardiology,the First Affiliated Hospital of South China University,Hengyang 421000,Hunan,China)

机构地区：[1]南华大学附属第一医院心血管内科,湖南衡阳421000

出　　处：《中国老年学杂志》2021年第8期1679-1682,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金项目(81870230);湖南省自然科学基金青年项目(2017JJ3278,2017JJ3271);湖南省研究生创新课题(CX20200973)。

摘　　要：目的观察外源性硫化氢(H_(2)S)对H型高血压大鼠心肌纤维化及c-Jun氨基末端激酶(JNK)信号通路的影响。方法取30只雄性自发性高血压(SHR)大鼠随机分为Model组、Model+H_(2)S组、茴香霉素(Anisomycin)组,并饮用1%L-蛋氨酸6 w建立H型高血压模型,20只同品系成年雄性WKY大鼠每天饮用等量清水随机分为:Control组、Control+H_(2)S组,建模成功后,Anisomycin组及Control+H_(2)S组大鼠均腹腔注射硫氢化钠〔NaHS,56μmol/(kg·d)〕,Anisomycin组大鼠在此基础上腹腔注射JNK激动剂Anisomycin,5 mg/(kg·d)。Control组和Model组大鼠均腹腔注射同等剂量的生理盐水。4 w后处死大鼠,通过Masson染色、Western印迹观察变化。结果与Control组相比,Model组、Anisomycin组心肌组织中心肌间质胶原纤维沉积明显增多,同时含半胱氨酸的天冬氨酸蛋白水解酶(caspase)-9、JNK蛋白表达水平明显升高(P<0.05);B细胞淋巴瘤(Bcl)2表达水平明显下降(P<0.05);与Model组、Anisomyci组相比,Model+H_(2)S组心肌间质胶原纤维沉积明显改善,同时caspase-9、JNK蛋白表达水平明显下降(P<0.05);Bcl2表达水平明显升高(P<0.05)。结论H_(2)S可改善H型高血压大鼠纤维化,其机制可能与通过JNK信号通路抑制细胞凋亡相关。Objective To investigate the effects of exogenous hydrogen sulfide(H_(2)S)on myocardial fibrosis and JNK signaling pathway in H-type hypertensive rats.Methods A total of 30 male SHR rats and 20 same strain adult male WKY rats were randomly divided into the following groups:control group,model group,model+H_(2)S group,anisomycin group,and control+H_(2)S group,respectively,in which SHR rats were randomly divided into model group,model+H_(2)S group,and anisomycin group,and drank 1%L-methionine for 6 weeks to establish H-type hypertension model,and WKY rats were randomly divided into control group and control+H_(2)S group,with free access to equal amount of water per day.The rats in model+H_(2)S group,anisomycin group and control+H_(2)S group were intraperitoneally injected with H_(2)S donor NaHS〔56μmol/(kg·d)〕,and the rats in anisomycin group were intraperitoneally injected with the agonist of JNK〔anisomycin,5 mg/(kg·d)〕in addition to NaHS.Rats in the control group and model group were intraperitoneally injected with saline at the same dose.After 4 weeks,the rats were sacrificed.Masson staining was applied to observe cardiac fibrosis.Western blot was employed to detect the changes of caspase-9,Bcl2 and JNK protein expression.Results Compared with the control group,the myocardial interstitial collagen fiber deposition in model group and anisomycin group was significantly increased,meanwhile the expression levels of caspase-9 and JNK protein were significantly increased(P<0.05);the expression level of Bcl2 was significantly decreased(P<0.05).Compared with model group and anisomyci group,the collagen fiber deposition in model+H_(2)S group was significantly improved,meanwhile the expression levels of caspase-9 and JNK protein were significantly decreased(P<0.05);the expression level of Bcl2 was significantly increased(P<0.05).Conclusions H_(2)S ameliorates fibrosis in H-type hypertensive rats,and its mechanism might be associated with inhibition of apoptosis through JNK signaling pathway.

关 键 词：硫化氢 细胞凋亡 JNK信号通路 心肌纤维化 H型高血压 

分 类 号：R972[医药卫生—药品]