兔动脉粥样硬化血管内皮细胞膜超微结构动态变化及他汀类药干预的影响

Dynamic changes of ultrastructure of endothelial cell membrane in rabbits with atherosclerosis and intervention of statins

目的:应用原子力显微镜(atomic force microscope,AFM)观察动脉粥样硬化(atherosclerosis,As)血管内皮细胞(vascular endothelialcell,VEC)膜超微结构的动态演变情况,以及探讨阿托伐他汀保护血管内皮功能的非降脂作用。方法:取88只新西兰纯种雄性大白兔,随机分为3组,对照组24只喂以普通兔饲料、高脂模型组32只喂以高脂饲料、药物组32只喂以高脂饲料同时给与阿托伐他汀,分别于2、4、6、8周末每组随机处死6-8只。取胸主动脉中段制作标本,应用AFM进行扫描。结果:对照组VEC呈梭形,排列规整,其长轴与血液流动方向一致。高脂模型组随时间不同内皮细胞发生了动态改变,细胞形态变成球形、不规则形、体积变大,排列紊乱。1μm、500nm扫描范围细胞膜超微结构也有明显的改变。药物组VEC的变化在相应的时间段明显好于高脂模型组,基本接近对照组。同时比较了三组500nm水平下膜蛋白的平均粗糙度(meanroughness,Ra),发现在高脂组明显高于正常对照组和药物组,具有统计学差异(P<0.01),阿托伐他汀组细胞膜粗糙度高于正常对照组(P<0.01)。结论:As形成过程中VEC膜超微结构发生了明显的动态变化,而阿托伐他汀可早期预防As引起的内皮细胞损伤,从而阻止As的进一步形成。

Objective： To observe the changes of membrane surface ultramicrostmcture of vascular endothelial cell （VEC） and investigate the interventional effect of statins in atherosclerosis（As）with atomic force microscope（AFM）. Methods： A total of 88 male New Zealand white rabbits were randomly divided into 3 groups：control group：24 rabbits were fed standard rabbit diet. As group：32 rabbits were fed cholesterol diet. atorvastatin group：32 rabbits were fed cholesterol diet and atorvastatin. By the end of2nd, 4th, 6th, 8th week 6-8 rabbits of each group were sacrificed and the middle segments of aortas were obtained to be observed with AFM. Results： The VECs of control group were fusiform shape and aligned regularly. Their macroaxis were parallelly with the direction of hemokinesis.VECs of changed as time. Their shapes were round, irregularity and so on. They aligned confused and their volumes changed swell. But the VECs ofatorvastatin group were better than those of As group. There were evident changes at the lure and 500nm scanning range on mem- brane surface ultramicrostructure of VECs of each group. Meanwhile, The mean roughness （Ra） of membrane protein of three groups were compared. The Ra of the atherosclerosis group was significantly higher than those of the control group and the atorvastatin group （P〈0.01）.And there was significant difference between the control group and the atorvastatin group（P〈0.01）. Conclusion： The membrane surface ultramicrostructure of VEC changed obviously during formation of atherogenesis and atorvastatin could prevent atherogenesis by protecting VEC.