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)、Ang Ⅱ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 Ang Ⅱ导致的αSMA、ACTA2和MYH11的表达下调，并抑制了 Ang Ⅱ诱导的SPP1和Vimentin蛋白表达。Ang Ⅱ组和Ang Ⅱ+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Ang Ⅱ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。
Investigate the mechanism of angiotensin Ⅱ induced aortic dissection based on G protein signaling modulator 2 knockout
Objective To investigate the role of G protein signal regulator 2(RGS2)in regulating the formation of angiotensin Ⅱ(Ang Ⅱ)-induced aortic dissection.Methods C57BL/6 mice were divided into 3 groups:control group(n=10),Ang Ⅱ group(n=20),Ang Ⅱ+sh-RGS2 group(n=20).The Ang Ⅱ group and Ang Ⅱ+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 coun-teracted Ang Ⅱ-induced inhibition of αSMA,ACTA2 and MYH11,and suppressed Ang Ⅱ-induced SPP1 and Vim-entin in VSMC.The incidence of aortic dissection in Ang Ⅱ group and Ang Ⅱ+sh-RGS2 group were 45％(9/20)and 10％(2/20),respectively.Fewer elastic lamina thickening,aortic rupture,and aortic wall collagen fiber con-tent were observed in Ang Ⅱ+sh-RGS2 group compared to Ang Ⅱ group.In addition,compared with the Ang Ⅱgroup,the maximum diameter of the aorta in the Ang Ⅱ+sh-RGS2 group was significantly reduced(P＜0.05).In addition,the ACTA2 and MYH11 proteins in the aorta of the Ang Ⅱ+sh-RGS2 group were significantly higher than those in the Ang Ⅱ group(P＜0.01),while the RGS2,SPP1,and Vimentin proteins significantly decreased(P＜0.01).Conclusion Knockdown of RGS2 inhibits the transformation of Ang Ⅱ-induced VSMC from a contractile phenotype to a synthetic phenotype,thereby reducing the incidence of aortic dissection formation.
regulator of G protein signaling 2angiotensin Ⅱaortic dissectionvascular smooth muscle cells
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