【摘要】 目的观察普罗布考对兔动脉粥样硬化模型高胆固醇血症、主动脉内皮功能及LOX-1表达的影响。方法新西兰大白兔随机分为正常对照组(普通饮食,6只),高脂饮食组(高脂饮食,10只)及普罗布考组(高脂饮食+普罗布考200mg/kg·d,10只)。实验开始前及第12周分别耳缘静脉采血测定血清总胆固醇。第12周处死动物,取胸主动脉,制备离体胸主动脉环对乙酰胆碱的反应以检查内皮功能,RT-PCR与免疫印迹检测凝集素样氧化低密度脂蛋白受体-1(LOX-1)基因与蛋白质表达水平。结果普罗布考可以显著降低兔动脉粥样硬化模型血清总胆固醇浓度;防止高脂血症兔胸主动脉对乙酰胆碱引起的内皮信赖性舒张(E-DR)反应明显降低;以及下调模型动脉主动脉明显增强了LOX-1表达。结论兔动脉粥样硬化模型内皮功能损伤的机制与LOX-1表达增强有关,普罗布考保护内皮功能可能的机制是下调LOX-1表达的作用。更多还原

【Abstract】 [Objective] The effects of probucol on total cholesterol concentrati on, endothelium-dependent vasodilator activity and repression of Lectinlike Oxid ized Low Density Lipoprotein Receptor-1(LOX-1) expression were tested in a NZW r abbit atherosclerosis model. [Methods] Twenty-six NZW rabbits were randomly di vided into three groups: a normal control group (fed on normal commercial rabbit diet, n =6), a hyperlipidemic group (fed on high-fat diet, n =10) and a probuco l treatment group (fed on high-fat diet and probucol 200 mg/kg·d, treatment n = 10). Plasma total cholesterol (TC) concentration at the beginning and the 12-wee k end point of the experiment determined, and all the experimental rabbits were sacrificed, and endothelial function test were performed on thoracic aortic ring s prepared from the isolated aorta using the vascular endothelium-dependent rela xation (EDR) parameter in response to acetylcholine The aortic atherosclerotic l esion expression of LOX-1 mRNA and protein were examined by RT-PCR and Western b lotting respectively. [Results] Probucol significantly lowered plasma TC level , protected endothelial function as indicated by the improvement of vascular EDR of aortic rings in response to acetylcholine, and repressed the LOX-1 mRNA and protein expression that were over-expressed in the atherosclerosis models. [Con clusion] Over-expression of LOX-1 might be one of the mechanism of endothelial dysfunction in atherosclerotic model and probucol repression of LOX-1 plays an i mportant role in improvement of endothelial function.更多还原