卡维地洛对兔颈动脉易损斑块与血管平滑肌细胞凋亡及基因表达的影响  

Effects of carvedilol on blood vessel smooth muscle cell apoptosis and gene expression in carotid atherosclerotic rabbits

作　　者：管耘园[1] 卢辉和[1] 叶炳华[1] 盛臻强[1] 王毅[1] 黄建飞[1] 金恒[1] 华守明[1] 杨其昌[1] 

机构地区：[1]南通大学第二附属医院,南通226001

出　　处：《中华老年心脑血管病杂志》2007年第10期696-699,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

摘　　要：目的探讨动脉易损斑块(VP)与血管平滑肌细胞(VSMC)凋亡的关系及卡维地洛稳定斑块的作用机制。方法将45只雄性日本大耳白兔随机分成5组,分别为正常对照组、卡维地洛组、美托洛尔组、单纯转染组和单纯拉伤组,每组9只。正常对照组给予普通饲料,其他组给予球囊损伤颈总动脉加高脂喂养,8周后,除单纯拉伤组,其他3组给予野生型p53基因转染颈总动脉,卡维地洛组和美托洛尔组分别加喂卡维地洛和美托洛尔,继续高脂饲料喂养4周;实验前、实验后8、12周分别测定血脂;实验结束后检测斑块VSMC凋亡率及bcl-2、bax、α平滑肌肌动蛋白(-αactin)的局部表达情况,并分析血管病理形态学。结果球囊损伤组均出现典型动脉粥样硬化斑块,与单纯转染组比较,美托洛尔组及卡维地洛组纤维帽厚度均明显增加,卡维地洛组更显著(P<0.01);卡维地洛和美托洛尔对血脂均无明显影响;卡维地洛组斑块中VSMC凋亡率、bax及bax/bcl-2比值下降,上调-αactin、bcl-2阳性表达(P<0.01)。结论卡维地洛稳定斑块作用优于美托洛尔,其机制可能在于卡维地洛除β受体阻断作用外还具有抑制VSMC凋亡的作用。Objectives To investigate the relationship between vulnerable atherosclerorotic plaque and apoptosis of vascular smooth muscle cell（VSMC）, and the mechanisms of carvedilol（CAR） in stabilizing atherosclerotic plaque. Methods Forty-five male Japanese white rabbits were divided randomly into 5 groups of 9 each. One group was fed with normal diet as blank control. In other four groups, the common carotid arteries of the rabbits fed with high CAR diet were injured by balloon. The common carotid arteries of 3 groups were transfected with wild type p53 gene 8 weeks later, then two groups of them were treated with CAR and metoprolol（MET） respectively, and high CAR diet was continued for other 4 weeks. The apoptosis rate of VSMC and the local ex- pression of bcl-2,bax,α-actin were examined after experiment. Results The typical carotid atherosclerorotic plaque was observed in balloon-injured groups. Compared with the rabbits receiving transfection only, the thickness of the fibrous cap in rabbits receiving CAR and MET was increased, especially in CAR group. Both CAR and MET had no obvious influence on the serum lipid. The apoptosis rate of VSMC, the local expression of bax gene and bax/bcl-2 ratio were decreased, and the expression rates of α-actin and bcl-2 gene were increased in CAR group. Conclusions Both CAR and MET can improve the stability of the plaque, but CAR is better. Its mechanisms may lie in that CAR has function of decreasing the apoptosis rate of VSMC in addition to its function of blocking β-receptor.

关 键 词：颈动脉疾病 转染 肌 平滑 血管 细胞凋亡 基因表达 卡维地洛 

分 类 号：R96[医药卫生—药理学]