平滑肌细胞caveolae在自发性高血压大鼠肾叶间动脉收缩功能改变中的作用研究  

Role of caveolae in smooth muscle cells-mediated enhanced vasoconstriction of interlobar renal artery to angiotensin Ⅱ in SHR rats

作　　者：张海军[1] 张茜[1] 谢小萍[1] 常耀明[1] 暴军香[1] 

机构地区：[1]陕西第四军医大学航空航天医学系航空航天卫生学教研室,西安710032

出　　处：《临床肾脏病杂志》2016年第10期625-631,共7页Journal Of Clinical Nephrology

基　　金：国家自然科学基金项目资助(NO.31071045;81401550)

摘　　要：目的探讨平滑肌细胞caveolae在自发性高血压大鼠(spontaneously hypertensive rat,SHR)肾叶间动脉对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)的收缩反应改变中的作用及其机制。方法采用Wistar Kyoto(WKY)大鼠作为对照组,SHR为实验组(两组大鼠均为Wistar京都种大鼠),分别对SHR和WKY大鼠采用血管环张力描记技术检测肾叶间动脉对AngⅡ的收缩反应,采用甲基-β-环糊精(methyl-beta-cyclodextrin,MCD)孵育以减少平滑肌细胞caveolae含量,采用电镜观察caveolae数量,采用荧光实时定量PCR(quantitative real-time PCR,qRT-PCR)及蛋白免疫印迹(Western blot)法检测血管紧张素受体1型(qngiotensin type 1 receptor,AT1R)的基因和蛋白表达,采用免疫沉淀和Westernblot检测caveoin-1与AT1R的结合。结果与WKY组大鼠相比,SHR组肾叶间动脉对AngⅡ的收缩反应强度及敏感性均明显增加(P<0.05),平滑肌细胞caveolae数量显著增加(P<0.05),MCD孵育可使SHR组肾叶间动脉对AmgⅡ的收缩强度部分恢复,使其敏感性恢复正常。与WKY组相比,SHR组肾叶间动脉的AT1R蛋白表达显著增加(P<0.05),AngⅡ作用后caveolin-1与AT1R的结合显著增强(P<0.05),MCD孵育后AT1R的蛋白表达降低,但仍高于WKY组,而caveolin-1与AT1R的结合恢复正常水平。结论平滑肌细胞caveolae增加参与介导SHR肾叶间动脉对AngⅡ收缩反应改变,其可能通过增加平滑肌ATIR含量以及caveolin-1与AT1R的结合而增强收缩反应强度及敏感性。Objective To investigate the role of caveolae in higher vasoconstriction of interlobar renal artery （IRA） of spontaneously hypertensive rat （SHR） to angiotensin Ⅱ（Ang Ⅱ）. Methods I- sometric force recording system was used to detect the vascular function. Methyl-beta-cyclodextrin （MCD） was employed to reduce the caveolae abundance. Real-time polymerase chain reaction （RT- PCR） and Western blotting were conducted to examine the expression of mRNA and protein of angio- tensin type 1 receptor （AT1R）. Immumoprecipitation followed by Western blotting was carried out to test the binding of caveolin-1 and AT1R. Results As compared to Wistar Kyoto （WKY） rats, the constriction of IRA to Ang Ⅱ was increased by 32. 7% in SHR （P〈0. 05）. Meanwhile, the abundance of caveolae on vascular smooth muscle cells （VSMCs） was enhanced significantly （P〈0. 05）. After reducing the caveolae by MCD, the intensity and sensitivity of vasoconstriction to Ang II in IRA of SHR were partly and entirely reversed, respectively. Moreover, ATIR protein expression was higher in IRA of SHR group than in WKY group in which the ATIR protein expression was lowered in part by MCD incubation. In IRA of both WKY group and SHR group, Ang II could promote the binding of AT1R to caveolin-1 （P（0. 05）, which was by a larger extent in SHR group than in WKY group （P〈0. 05）. After treatment with MCD, the binding of the two proteins in IRA of SHR group was restored to the level of WKY rats. Conclusions Caveolae regulates the enhanced intensity and sensitivity of vasoconstriction to Ang Ⅱ in IRA of SHR by raising AT1R protein content and binding of AT1R to eaveolin-1.

关 键 词：自发性高血压大鼠 CAVEOLAE 肾叶间动脉 收缩反应 血管紧张素Ⅱ 

分 类 号：R544.1[医药卫生—心血管疾病]