血管平滑肌细胞表型转化在高盐诱导的大鼠颈动脉重构中的作用  

The Role of Phenotype Transformation of Vascular Smooth Muscle Cells in High Salt-induced Carotid Artery Remodeling of Wistar Rats

作　　者：胡从智 商黔惠[1,2] 刘婵[1] 刘娟[1] 赵宇[1,3] 王晓春[1] 

机构地区：[1]遵义医学院临床医学研究所心血管病研究所高血压研究室 [2]遵义医学院附属医院心内科 [3]遵义医学院附属医院内分泌科,贵州省遵义市563003

出　　处：《中国动脉硬化杂志》2016年第5期433-439,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81160041和81460077);贵州省社会发展攻关计划项目[黔科合SY字(2011)3047号]

摘　　要：目的探讨血管平滑肌细胞发生表型转化在高盐饮食诱导的Wistar大鼠颈动脉重构中的作用以及替米沙坦的干预效应。方法雄性Wistar大鼠随机分为对照组(0.5%Na Cl饲料饲养)、高盐模型组(4%Na Cl饲料饲养)和替米沙坦组(替米沙坦+4%Na Cl饲料饲养),共喂养24周。HE染色和Masson染色观察颈动脉中膜形态结构的变化。通过real-time PCR和免疫组织化学法测定α-平滑肌肌动蛋白(α-SMA)、平滑肌22α(SM22α)、骨桥蛋白(OPN)的mRNA和蛋白在颈动脉的表达。结果与比照组比较,高盐模型组大鼠的血压明显升高(P<0.05),颈动脉中膜增厚、中膜厚度/腔径比、血管壁横截面积、中膜胶原容积分数增加,增殖细胞核抗原(PCNA)阳性表达明显增加(P<0.01),α-SMA、SM22α的蛋白和mRNA表达明显降低,而OPN的蛋白和mRNA表达升高;与高盐模型组比较,替米沙坦组大鼠的血压降低,颈动脉中膜厚度和血管壁横截面积减少、中膜胶原容积分数降低、PCNA阳性表达率减少(P<0.01),α-SMA、SM22α的蛋白及mRNA表达升高,而OPN的蛋白和mRNA表达降低。结论 4%高盐饮食可引起Wistar大鼠颈动脉重构和血压升高,其机制之一可能为血管平滑肌细胞在高盐的作用下发生了由收缩型向合成型转变的表型转化;替米沙坦能够抑制血管平滑肌细胞发生表型转化,并改善颈动脉重构。Aim To investigate the role of vascular smooth muscle cell phenotype transformation in carotid artery remodeling of Wistar rats fed by high salt diet,and the intervention of telmisartan. Methods The male Wistar rats were randomly divided into control group（ 0. 5%Na Cl feed）,model group（ 4%Na Cl feed）,telmisartan group（ 4%Na Cl and telmisartan 5 mg /（ kg·day） feed）. After 24 weeks,changes of morphology and structure of carotid artery were investigated by HE staining and Masson staining. The mRNA and protein levels of α-smooth muscle actin（ α-SMA）,smooth muscle 22α（ SM22α） and osteopontin（ OPN） were analyzed by quantitative real-time PCR and immunohistochemical staining. Results Compared with the control group,the blood pressure,media thickness,cross-sectional area,collagen volume fraction,and proliferating cell nuclear antigen（ PCNA） positive cells were elevated in the model group. At the same time,the model group showed an increase in the mRNA and protein levels of α-SMA,SM22α,and a decrease of OPN. The telmisartan reduced the blood pressure,media thickness,cross-sectional area,collagen volume fraction,and the expression of PCNA and OPN,compared with the model group. Moreover,the mRNA and protein levels of α-SMA,SM22α were upregulated by telmisartan. Conclusions The 4% high salt diet can cause carotid artery remodeling and elevated-blood pressure in Wistar rats. The vascular smooth muscle phenotype transformation might be involved in the mechanism of carotid artery remodeling induced by high salt. Telmisartan can prevent artery remodeling partially via regulating vascular smooth muscle cell phenotypic transformation.

关 键 词：高盐饮食 高血压 颈动脉重构 表型转化 

分 类 号：R363[医药卫生—病理学]