基于G蛋白信号调节因子2敲低探讨血管紧张素Ⅱ诱导的主动脉夹层形成的机制  

Investigate the mechanism of angiotensinⅡinduced aortic dissection based on G protein signaling modulator 2 knockout

作　　者：王庆功 薛雅萍 孙海霞[1] 曹宁[1] Wang Qinggong;Xue Yaping;Sun Haixia;Cao Ning(Cardiovascular Ultrasound Room,Qinghai Provincial People′s Hospital,Xining 810007)

机构地区：[1]青海省人民医院心血管超声室,西宁810007

出　　处：《安徽医科大学学报》2024年第7期1188-1194,共7页Acta Universitatis Medicinalis Anhui

基　　金：青海省卫生健康委员会科研项目(编号:202122315)。

摘　　要：目的探讨G蛋白信号调节因子2(RGS2)在调节血管紧张素Ⅱ(AngⅡ)诱导的主动脉夹层形成中的作用。方法将C57BL/6小鼠分为3组:Control组(n=10)、AngⅡ组(n=20)、AngⅡ+sh-RGS2组(n=20)。AngⅡ组和AngⅡ+sh-RGS2组小鼠建立了主动脉夹层模型。在体内评估主动脉夹层的发生率,在体外和体内评估血管平滑肌细胞(VSMC)表型转化。结果RGS2的敲低逆转了AngⅡ导致的αSMA、ACTA2和MYH11的表达下调,并抑制了AngⅡ诱导的SPP1和Vimentin蛋白表达。AngⅡ组和AngⅡ+sh-RGS2组的主动脉夹层发生率分别为45%(9/20)和10%(2/20)。与AngⅡ组小鼠比较,AngⅡ+sh-RGS2组小鼠中观察到更少的弹性层增厚、主动脉破裂和主动脉壁胶原纤维含量。此外,与AngⅡ组比较,AngⅡ+sh-RGS2组主动脉的最大直径减小(P<0.05),ACTA2、MYH11蛋白增加(P<0.01),RGS2、SPP1、Vimentin蛋白降低(P<0.01)。结论RGS2敲低抑制AngⅡ诱导的VSMC从可收缩表型转变为合成表型,降低了主动脉夹层形成的发生率。Objective To investigate the role of G protein signal regulator 2(RGS2)in regulating the formation of angiotensinⅡ(AngⅡ)-induced aortic dissection.Methods C57BL/6 mice were divided into 3 groups:control group(n=10),AngⅡgroup(n=20),AngⅡ+sh-RGS2 group(n=20).The AngⅡgroup and AngⅡ+sh-RGS2 group established an aortic dissection model.The incidence of aortic dissection was evaluated in vivo,and the phenotypic transformation of VSMC was evaluated in vitro and in vivo.Results Knockdown of RGS2 largely counteracted AngⅡ-induced inhibition ofαSMA,ACTA2 and MYH11,and suppressed AngⅡ-induced SPP1 and Vimentin in VSMC.The incidence of aortic dissection in AngⅡgroup and AngⅡ+sh-RGS2 group were 45%(9/20)and 10%(2/20),respectively.Fewer elastic lamina thickening,aortic rupture,and aortic wall collagen fiber content were observed in AngⅡ+sh-RGS2 group compared to AngⅡgroup.In addition,compared with the AngⅡgroup,the maximum diameter of the aorta in the AngⅡ+sh-RGS2 group was significantly reduced(P<0.05).In addition,the ACTA2 and MYH11 proteins in the aorta of the AngⅡ+sh-RGS2 group were significantly higher than those in the AngⅡgroup(P<0.01),while the RGS2,SPP1,and Vimentin proteins significantly decreased(P<0.01).Conclusion Knockdown of RGS2 inhibits the transformation of AngⅡ-induced VSMC from a contractile phenotype to a synthetic phenotype,thereby reducing the incidence of aortic dissection formation.

关 键 词：G蛋白信号调节因子2 血管紧张素Ⅱ 主动脉夹层 血管平滑肌细胞 

分 类 号：R782[医药卫生—口腔医学]