低切应力对高血压颈动脉血管重构作用的影响及其信号转导机制  

RhoA/ROCK/MAPKs signal transduction pathway involved in carotidartery remodeling in hypertension induced by low shear stress

作　　者：刘伟[1] 关智媛 王静[1] 郑婷[1] 

机构地区：[1]兰州大学第二医院神经内科,甘肃兰州730030 [2]兰州大学第二临床医学院,甘肃兰州730030

出　　处：《中国生物制品学杂志》2017年第8期824-827,832,共5页Chinese Journal of Biologicals

基　　金：甘肃省省青年科技基金计划项目(1506RJYA246)

摘　　要：目的观察低切应力对高血压颈动脉血管重构作用的影响,并初步探讨其信号转导机制。方法分离猪右侧颈总动脉,建立血管体外培养模型,实验分为高切应力组(切应力20 dyn/cm^2,对应灌洗液的流量为200 ml/min)、低切应力组(5 dyn/cm^2,对应灌流液的流量为50 ml/min)及对照组(未经培养的新鲜血管)。镜下测量颈动脉内径及壁厚度,并计算壁横截面积;TUNEL法检测切应力对体外培养猪颈总动脉血管平滑肌细胞凋亡影响;Western blot法检测切应力对体外培养猪颈总动脉血管组织中RhoA、P-MYPT-1、P-ERK1/2、P-JNK和P-P38蛋白表达影响。结果与对照组和高应力组比较,低应力组血管壁厚度和壁横截面积明显增加(P<0.05),血管内径明显变小(P<0.05),内径/壁厚比值明显降低(P<0.05);血管平滑肌细胞TUNEL染色阳性细胞明显增多(P<0.05),凋亡率显著增加(P<0.05);血管组织中RhoA、P-MYPT-1、P-ERK1/2、P-JNK和P-P38蛋白的表达水平明显升高(P<0.05)。结论低切应力对体外培养高血压颈动脉血管重构具有显著地诱导作用,其机制可能与其激活RhoA/ROCK信号,从而引起胞质内丝裂原活化蛋白激酶家族(MAPKs)的3个成员(ERK1/2、JNK、P38)的磷酸化反应有关。Objective To observe the effect of low shear stress on the remodeling of carotid artery in hypertension and investigate the potential signal transduction mechanism. Methods The reconstruction model of carotid artery hypertension in vitro was established by separation of right common carotid artery of pigs. The carotid arteries were divided into high（20 dyn/cm^2） and low（5 dyn/cm^2） shear stress groups, using those uncultured as control. The flows of perfusate for high and low shear stress groups were 200 and 50 ml/min respectively. Lumen diameter, vascular wall thickness were measured by microscopy, and the cross-sectional area was calculated. The effect of shear stress on apoptosis of vascular smooth muscle cells of pig carotid artery cultured in vitro was evaluated by TUNEL method. The expressions of RhoA, P-MYPT-1, P-ERK1/2, P-JNK and P-P38 proteins in vascular tissue of pig carotid artery cultured in vitro were determined by Western blot. Results Compared with those in control and high shear stress groups, the vascular wall thickness and cross-sectional area in low stress group increased significantly（P〈0. 05）, while the diameter of the blood vessel decreased significantly（P〈0. 05）, the ratio of the inner diameter to the wall thickness decreased significantly（P〈0. 05）, the number of TUNEL positive cells increased significantly（P〈0. 05）, the apoptosis rate of vascular smooth muscle cells increased significantly（P〈0. 05）, and the expression levels of RhoA, P-MYPT-1, P-ERK1/2, P-JNK and P-P38 proteins increased significantly（P〈0. 05）. Conclusion Low shear stress significantly induced the carotid artery vascular remodeling in hypertension, of which the mechanism might be associated with the activation of RhoA/ROCK signal thereby causing the phosphorylation of three members（ERK1/2, JNK and P38）of mitogen-activated protein kinase（MAPK）family.

关 键 词：低切应力 高血压 颈动脉 血管重构 信号转导 

分 类 号：R543.15[医药卫生—心血管疾病]