动脉粥样硬化兔主动脉血管壁机械敏感性离子通道蛋白Piezo1表达与血管内膜厚度相关性分析

Correlation between Piezo1 expression and intimal thickness of the aortic wall in atherosclerotic rabbits

目的通过建立兔动脉粥样硬化模型,分析其主动脉血管壁机械敏感性离子通道蛋白Piezo1表达水平与血管内膜厚度的相关性。方法将32只健康新西兰大白兔按随机分组法分为对照组8只、AS模型组24只,对照组给予普通饲料喂饲,AS模型组给予高脂饲料喂饲,共12周。于造模前、造模后4、8、12周每组各处死2只实验兔,取主动脉弓处血管壁组织,采用HE染色进行组织形态学观察,OLYSIA软件测定血管内膜厚度,ELISA法检测机械敏感性离子通道蛋白Piezo1的表达。结果对照组主动脉分层清楚,内膜无增厚;AS模型组随着建模时间延长,主动脉管壁内点状突起增多,内膜增厚,含许多泡沫细胞及脂质沉积。与对照组同时点比较,AS模型组造模后各时点血管内膜厚度、Piezo1表达水平均增加;与造模前比较,AS模型组造模后各时点血管内膜厚度、Piezo1表达水平均增加(P均<0.05)。Pearson相关分析显示,造模4、8、12周血管内膜厚度与Piezo1表达均呈正相关(r=0.53,P=0.043;r=0.65,P=0.038;r=0.78,P=0.025)。结论在AS的发生发展中,兔主动脉血管壁机械敏感性离子通道蛋白Piezo1表达水平与血管内膜厚度呈正相关,通道蛋白Piezo1可能通过影响血管内皮细胞形态引起血管重构,从而参与AS的发生发展。

Objective To analyze the correlation between the expression level of piezo-type mechanosensitive ion channel component 1(Piezo1)and intimal thickness through establishing a rabbit atherosclerosis(AS)model.Methods A total of 32 healthy New Zealand white rabbits were randomly divided into the control group(n=8)and AS model group(n=24).The rabbits in the control group were given normal diet,while the rabbits in the AS model group were given high-fat diet,both for 12 weeks.Two experimental rabbits each were sacrificed before and 4,8,and 12 weeks after modeling in both groups.The vessel wall tissues in the aortic arch were collected and stained with hematoxylin and eosin for histomor⁃phological observation.Software OLYSIA was used to determine the intimal thickness.ELISA was used to determine the Piezo1 protein expression.Results In the control group,the aorta was clearly stratified and the intima was not thick⁃ened.In the AS model group,the aortic wall showed increased punctate protuberances,intimal thickening,and many foam cells and lipid deposits over modeling time.Compared with the control group,the AS model group had significantly higher intimal thickness and Piezo1 expression level at each time point(all P<0.05).Compared with baseline level,the AS model group had significantly increased intimal thickness and Piezo1 expression level at each time point after modeling(both P<0.05).The Pearson correlation analysis showed that intimal thickness was positively correlated with Piezo1 expression at 4,8,and 12 weeks after modeling(r=0.53,P=0.043;r=0.65,P=0.038;r=0.78,P=0.025).Conclusions During the development and progression of atherosclerosis,there is a positive correlation between the expression level of Piezo1 protein and intimal thickness in the rabbit aortic wall.Piezo1 can cause vascular remodeling by affecting the morphology of vascular endothelial cells,thus participating in the development and progression of atherosclerosis.