氯沙坦对动脉粥样硬化兔的MCP-1及基因表达的实验研究

为了探讨血管紧张素Ⅱ的Ⅰ型受体(AT1R)拮抗剂氯沙坦(Losartan)的抗动脉粥样硬化(AS)作用及观察其是否能抑制单核细胞趋化蛋白-1(MCP-1)的蛋白及基因表达,我们通过高脂饮食及内皮损伤术建立兔AS模型,一组用Losartan(25mg/kg/d),另一组不用,喂养4个月,观察血管内膜的变化;同时做免疫组化及原位杂交,分别观察MCP-1蛋白及基因的表达。结果发现Losartan治疗组兔主动脉内膜面积及内、中膜面积之比均小于未治疗组,其MCP-1的蛋白及mRNA的表达亦明显减少,表明Losartan可通过抑制MCP-1的产生而具有抗AS作用。

An Experimental Study in the Effect in the Effect of Losartan on the Expresstion of MCP-1 and Its mRNA in a Rabbit Model of Atherosclerosis

To investigate the role of angiotensin II type l receptor antagonist Losartan on the protein and mRNA expres-sions of monocyte chemoattractant protein-1 (MCP-1 )in a rabbit model of atherosclerosis (AS ) , AS was induced in the aortic arteries of rabbits by endothelial damages and by feeling of atherogenic diets for 4 months, meanwhile, animals were randomized to receive treatment with Losartan (25 mg/kg/d )or receive no treatment, and killed after 4 months of treatment. The changes in the intimal area of blood vessels were demonstrated by immuno-histochemical techniques and the in situ hybridization technique to observe the expressions of MCP-1 and its mRNA. It was found that in the treated group of animals, intimal areas and the ratios of intimal area and the medial areas were diminished, while the expres-sions of MCP-1 protein and its genes were significantly reduced. These results suggest that Losartan could depress the production of MCP-1, contributing to its anti-atherosclerotic effectiveness in the rabbit model.