阿托伐他汀对兔动脉粥样硬化血管内皮细胞膜超微结构影响的研究

目的探讨纳米水平上阿托伐他汀对兔动脉粥样硬化(atherosclerosis,AS)血管内皮细胞(vascular endothelial cell,VEC)超微结构的影响。方法44只♂新西兰大白兔,随机分为3组,对照组12只,高脂组16只,阿托伐他汀组16只,分别于2、6wk末随机抽取6~8只处死,采血检测血脂,取胸主动脉制作标本,应用原子力显微镜(atomic force micro-scope,AFM)观察。结果AFM50μm大范围扫描可见对照组VEC呈梭形,大小约11.96μm×3.72μm。排列规则,其长轴与血流方向一致;高脂组2、6wk末兔VEC较正常对照组明显变大肿胀,变形,排列紊乱。500nm超微结构扫描正常组细胞膜蛋白由圆形、椭圆形的隆起构成,大小基本一致,隆起光滑饱满,隆起间界线分明;2、6wk高脂组内皮细胞膜蛋白由许多大小不一的隆起构成,形态各异,隆起表面凹凸不平,隆起间有许多孔洞,隆起间界限模糊;阿托伐他汀组2、6wk末VEC超微结构明显改善,更接近正常对照组。同时比较了3组500nm水平下膜蛋白的平均粗糙度(mean roughness,Ra),发现在2、6wk高脂组明显高于正常对照组和药物组,差异具有统计学意义(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AFM可直观的观察到AS受损的VEC及细胞膜的超微结构改变,以及阿托伐他汀明显改善AS引起的VEC损伤,从而发挥其降脂外的抗AS作用。

Effect of atorvastatin on the ultramicrostructure of the endothelial cell membrane in atherosclerotic rabbits: observed by atomic force microscope

Aim To explore the influence of atorvastatin on the ultramicrostructure of the membrane surface of the rabbit endothelial cells in rabbit atherosclerosis(AS)in the nanometer level.Methods A total of 44 male New Zealand white rabbits were randomly divided into 3 groups:control group consisting of 12 rabbits,AS group consisting of 16 rabbits and atorvastatin group consisting of 32 rabbits.By the end of 2nd,6th week 6~8 rabbits of each group were sacrificed and the middle segments of thoracic aortas were obtained to be observed with atomic force microscope.Results The control group vascular endothelial cells(VECs)were fusiform in shape and aligned regularly.Their size were about 11.96 μm×3.72 μm and their macroaxis were in parallel with the direction of hemokinesis.VECs in the atherosclerotic group were in deformity and bigger than those of the control group.They aligned irregularly and their volumes changed to be swelled.The membrane protein of VECs in the control group was composed of many round and elliptical eminences,which were almost in the same size.and with distinct boundary lines.The membrane protein of VECs in the atherosclerosis group was composed of many irregular eminences in different size.It was vague among the eminences in which there were many holes.But the VECs of atorvastatin group were better than those of atherosclerosis group.The ultramicrostructure of the membrane surface of the atorvastatin group VECs was obviously improved.Meanwhile,the mean roughness(Ra)of membrane protein of three groups was compared.The Ra of the atherosclerosis group was significantly higher than that 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).Conclusions The changes of the ultramicrostructure of the membrane surface of the damaged VECs in AS were directly observed by AFM.Atorvastatin could improve the damage of VECs so that it could prevent AS.