RhoA/Rho激酶1及肌球蛋白轻链磷酸化下调诱发主动脉夹层  

Decline of RhoA/Rho-kinase 1 expression and myosin light chain phosphorylation facilitate the formation of aortic dissection

作　　者：张薇 刘斐 舒晓龙 王恩慈 王利新 符伟国 Zhang Wei;Liu Fei;Shu Xiaolong;Wang Enci;Wang Lixin;Fu Weiguo(Department of Vascular Surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Vascular Surgery,Xiamen Branch,Zhongshan Hospital,Fudan University,Xiamen 361015,China)

机构地区：[1]复旦大学附属中山医院血管外科,上海200032 [2]复旦大学附属中山医院厦门医院血管外科,361015

出　　处：《中华实验外科杂志》2020年第5期828-831,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(81570438)。

摘　　要：目的:探讨RhoA/Rho激酶1(ROCK1)下调抑制肌球蛋白轻链(MLC)磷酸化在主动脉夹层(AD)形成过程中的作用。方法:检测正常(NA)和AD主动脉原代平滑肌细胞(SMC)中RhoA/ROCK1的表达与MLC的磷酸化程度。免疫荧光观察SMC中MLC磷酸化程度和结构。β-氨基丙腈(BAPN)联合应用ROCK1抑制剂Fasudil,验证RhoA/ROCK1下调在AD形成中的作用。组间比较采用 t检验或 χ2检验,Kaplan-Meier生存曲线采用非参数检验。 结果:NA组和AD组年龄( t=-1.439, P>0.05)、性别( χ2=0.900, P>0.05)差异无统计学意义,AD组高血压患者多于正常组( χ2=5.562, P<0.05)。AD主动脉SMC中RhoA(NA:42 782±31 339,AD:6 975±3 130, t=2.585, P<0.05)和ROCK1表达下调(NA:64 626±38 822,AD:13 851±961, t=2.977, P<0.05),MLC磷酸化减少(NA:230 193±27 749,AD:51 142±48 151, t=6.561, P<0.01)。免疫荧光显示AD组SMC和Fasudil处理的SMC中MLC磷酸化降低,结构受损。Fasudil联合BAPN的夹层形成率(100%)高于BAPN的夹层形成率(50%, χ2=22.780, P<0.01)。 结论:RhoA/ROCK1下调抑制MLC磷酸化促进了AD的发生。Objective To explore the role of RhoA/Rho-kinase 1(ROCK1)downregulation with myosin light chain(MLC)phosphorylation decline in the formation of aortic dissection(AD).Methods The expression of RhoA,ROCK1 and phosphorylation of MLC in the primary smooth muscle cell(SMC)isolated from the normal and AD aorta were detected.The phosphorylation and structure of MLC in the SMC were observed through immunofluorescence.Fasudil,inhibitor of ROCK1,was combined withβ-aminopropionitrile(BAPN)to identify the role of RhoA/ROCK1 and MLC phosphorylation in the formation of AD.Statistical analyses was conducted with SPSS 25.0.The quantitative variations were presented using Mean±SD.Results No significant difference was found in respects of age(t=-1.439,P>0.05)or gender(χ2=0.900,P>0.05)between NA and AD groups,while the number of hypertension was higher in the AD group(χ2=5.562,P<0.05).The expression of RhoA(NA:42782±31339,AD:6975±3130,t=2.585,P<0.05),ROCK1(NA:64626±38822,AD:13851±961,t=2.977,P<0.05),and phosphorylation of MLC(NA:230193±27749,AD:51142±48151,t=6.561,P<0.01)all declined in AD group.Immunofluorescence showed decreased phosphorylated MLC in AD SMC and normal SMC treated by Fasudil,with the structure impaired.Combined fasudil and BAPN lead to 100%formation of AD,significantly higher than 50%with sole BAPN(χ2=22.780,P<0.01).Conclusion The downregulation of RhoA/ROCK1 with declined MLC phosphorylation facilitates the formation of AD.

关 键 词：主动脉夹层 RHOA Rho激酶1 肌球蛋白轻链 

分 类 号：R543.1[医药卫生—心血管疾病]