TGF-β1/Smad通路在血管紧张素Ⅱ下调缝隙连接蛋白43表达中的作用  

Role of TGF-β1/Smad signaling in angiotensin Ⅱ mediated down-regulation of connexin 43

作　　者：侯婧瑛[1] 周长青[1] 郑韶欣[2] 郭天柱[1] 龙会宝[1] 伍权华[1] 钟婷婷[1] 王彤[1] 

机构地区：[1]中山大学孙逸仙纪念医院急诊科,广东广州510120 [2]中山大学孙逸仙纪念医院心内科,广东广州510120

出　　处：《中国病理生理杂志》2016年第10期1729-1736,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81270213;No.81070125);广东省科技计划(No.2010B031600032;No.2014A020211002);高校基本科研业务费中山大学青年教师重点培育项目(No.13ykzd16);广东省医学科研基金(No.A2016264)

摘　　要：目的:分析心肌梗死(MI)后心脏组织中血管紧张素Ⅱ(AngⅡ)、缝隙连接蛋白43(Cx43)和转化生长因子β1(TGF-β1)/Smad通路相关因子的变化情况,以探讨AngⅡ能否经由TGF-β1/Smad调节Cx43的表达。方法:采用左前降支冠状动脉(LAD)结扎建立大鼠心肌梗死模型后,20只SD雄性大鼠随机分为氯沙坦(20 mg·kg^(-1)·d^(-1))治疗组与MI组,分别于结扎后及治疗2周后检测心功能情况,并检测治疗2周后左室心肌组织不同区域AngⅡ、AngⅡ1型受体(AT1)、Cx43以及TGF-β1/Smad通路相关分子的变化情况。结果:氯沙坦组左室舒张末期内径(LVIDd)和左室收缩末期内径(LVIDs)明显缩小(P<0.01),室间隔厚度(IVSd)及左室后壁厚度(LVPWd)明显减小(P<0.05),左室射血分数(LVEF)显著增加(P<0.01);梗死区和边缘区的AngⅡ水平明显降低;梗死区AT1表达显著降低;Cx43在心肌组织不同区域表达增高,TGF-β1、Smad 2、Smad 3在心肌组织不同区域表达均降低,而Smad 7表达增高。结论:心肌梗死后AngⅡ激活可能通过作用于TGF-β1/Smad通路导致Cx43表达下调。AIM：To analyze the alterations of angiotensin Ⅱ （Ang Ⅱ）, connexin 43 （Cx43）, angiotenisinⅡreceptor type 1 （AT1） and signaling molecules in the TGF-β1/Smad pathway in different regions of the left ventricular heart tissue for exploring whether Ang Ⅱregulates Cx43 expression via the TGF-β1/Smad signaling pathway in myocardial infarction （ MI） rats.METHODS：MI was induced in 20 male Sprague-Dawley rats by the left anterior descending coronary artery ligation.The rats were then randomized into 2 groups.In the losartan group,20mg·kg^-1·d^-1 of losartan were administered for 2 weeks.Heart functions were assessed after surgery and 2 weeks later again following the above treatments . All the rats were sacrificed and relevant molecules , including Ang Ⅱ, AT1, and Cx43 were determined thereafter in different areas of the left ventricle .TGF-β1 and its downstream signaling molecules , including Smad 2, Smad 3 and Smad 7, were also detected .RESULTS：In losartan group , both left ventricular internal dimension diastole （ LVIDd） and left ventricular internal dimension systole （LVIDs） were smaller, with diminished interventricular septal thickness （IVSd） and left ventricular posterior wall depth （ LVPWd ） and distinct improvement of left ventricular ejection fraction （ LVEF ） （ P〈0.05 ） .Losartan therapy exhibited a reduction of Ang Ⅱin the infarct zone and the border zone in the cardiac tissues .AT1 was obviously attenuated in the infarct zone with an enhanced expression of Cx 43, which was also elevated in the border zone and none infarct zone .TGF-β1, Smad 2 and Smad 3 were decreased in different zones of the left ventricle , while Smad 7, in contrary to the above factors , presented a converse alteration .CONCLUSION：The activation of Ang Ⅱprovokes downregulation of Cx 43 through TGF-β1/Smad signaling pathway in MI rats .

关 键 词：血管紧张素Ⅱ 缝隙连接蛋白43 转化生长因子-Β1 SMAD 心肌梗死 

分 类 号：R363[医药卫生—病理学]