硫化氢调节缝隙连接蛋白表达改善高血压大鼠胸主动脉重构的治疗作用研究  

The therapeutic effect of hydrogen sulfide on arterial remodeling in the thoracic aorta of spontaneously hypertensive rats by the regulation of connexins expression

作　　者：李玲[1] 张亮[2] 马克涛[2] LI Ling;ZHANG Liang;MA Ketao(Medical Teaching and Experimental Center,School of Medicine,Shihezi University,Shihezi,Xinjiang 832000,China;Department of Physiology,School of Medicine,Shihezi University,Shihezi,Xinjiang 832000,China)

机构地区：[1]石河子大学医学院医学教学实验中心,新疆石河子832000 [2]石河子大学医学院生理学教研室,新疆石河子832000

出　　处：《石河子大学学报（自然科学版）》2020年第6期746-752,共7页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81600325)。

摘　　要：目的观察H 2S供体硫氢化钠(NaHS)调节缝隙连接蛋白(Connexins,Cxs)的表达对自发性高血压大鼠(spontaneously hypertensive rats,SHR)胸主动脉血管重构的保护作用。方法16只8周龄雄性SHR随机分为SHR对照组及SHR+NaHS干预组(n=8),8只Wistar京都(WKY)大鼠为正常对照组,SHR+NaHS组大鼠腹腔注射NaHS(56μmol/kg/d)干预8周,SHR对照组与和WKY组注射等量NaCl溶液。干预8周后采用测量尾动脉血压;ELISA测量各组大鼠胸主动脉中H 2S含量;HE与Masson染色评估胸主动脉血管增厚和胶原沉积;采用IHC法及Western blot检测胸主动脉中Cxs和血管平滑肌表型转换标志蛋白的表达。结果NaHS干预8周后可通过提高体内H 2S含量(P<0.05)使SHR动脉血压显著降低(P<0.05),并能通过增强SHR胸主动脉中Cx37、Cx43和Cx45的表达水平(P<0.05)而显著改善SHR胸主动脉中膜增厚(P<0.05)、胶原沉积(P<0.05)及缓解血管平滑肌表型转换标志蛋白(α-SMA、PCNA和OPN)的异常表达(P<0.05),且NaHS对SHR胸主动脉中Cx40表达及Cx43磷酸化水平的上调亦具有增强效应(P<0.05)。结论H 2S供体干预可通过调节SHR胸主动脉中Cxs表达而改善SHR动脉重构和胶原沉积,最终对高血压造成的血管结构损伤起到治疗作用。Objective This study was designed to determine if Hydrogen Sulfide(H 2S)donor(Sodium hydrosulfide,NaHS)can prevent arterial remodeling caused by hypertension in spontaneously hypertensive rats(SHR)via regulating Connexins(Cxs)in thoracic aorta of SHR.Methods Sixteen male SHR at 8 weeks of age were randomly divided into 2 groups(n=8 in each group):SHR control and SHR+NaHS.Equal numbers of male Wistar-Kyoto rats(WKYs)with the same age served as normotensive controls(WKY group,n=8).SHR in the SHR+NaHS group were intraperitoneally injected with 56μmol•kg-1•d-1 of NaHS at the same time daily for 8 weeks;SHR control and WKY rats were intraperitoneally injected with the same volume of normal saline once daily over the same time period.After treatment with drug,the tail arterial blood pressure was measured by the tail-cuff method;H 2S content in thoracic aorta was determined using ELISA.Hematoxylin and eosin and Masson′s trichrome staining were used to show aorta thickening and collagen accumulation in aorta,respectively.The expression of Cxs and several markers associated with vascular smooth muscle phenotypic switching in the thoracic aorta were analyzed using immunohistochemical staining and western blot.Results NaHS treatment for 8 weeks significantly reduced the elevation of arterial blood pressure through increasing the H 2S level(P<0.05)in the thoracic aorta of SHR(P<0.05);chronic NaHS administration also signi cantly ameliorated medial thickening(P<0.05),collagen deposition(P<0.05),and markedly attenuated the aberrant expression of several markers(α-SMA、PCNA and OPN)associated with vascular smooth muscle phenotypic switching(P<0.05)in the thoracic aorta of SHR via up-regulating the protein expression of Cx37,Cx43 and Cx45 in aorta.In addition,Exogenous NaHS increased hypertension-induced Cx40 expression and phosphorylated Cx43 protein expression in the thoracic aorta from SHR(P<0.05).Conclusions H 2S donor intervention can mitigated the arterial remodeling and collagen deposition in the thoracic aorta o

关 键 词：高血压 动脉重构 硫化氢 缝隙连接蛋白 

分 类 号：R544.1[医药卫生—心血管疾病]