Carriporide对高脂饮食所致兔动脉粥样硬化的保护作用

The Effects of HOE642 Against Atherosclerosis Induced by High Lipid Diet in Rabbits

为探讨钠 -氢交换体是否介导动脉粥样硬化的发生 ,在高脂饮食诱导的兔动脉粥样硬化模型上观察了选择性钠 -氢交换抑制剂Cariporide的抗动脉粥样硬化作用。 2 2只雄性新西兰兔随机分为 3组 :对照组给予普通饲料 ;模型组给予高脂饲料 ;治疗组给予高脂饲料的同时每天口服Cariporide 0 .1mg/kg。在高脂饲养前、治疗第 5和第 10周分别称重和取血检测血清总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇。 10周后处死动物 ,取出主动脉弓和心脏等 ,在光学显微镜和透射电子显微镜下行病理学检查。结果发现 ,对照组胸主动脉内膜表面光滑完整 ,光镜和电镜下内膜、内膜下层及中层未见异常改变。模型组动脉内膜增厚 ,内皮细胞损伤 ,管腔变窄 ,内膜下及中膜有大量泡沫细胞 ,平滑肌细胞排列紊乱 ;内弹力膜水肿 ,结构破坏。治疗组除一例发现主动脉管腔内膜有一隆起病灶外 ,其余兔主动脉内膜无明显损伤 ,内膜下层只有少量脂质侵入 ,内弹力膜完好 ,平滑肌细胞接近正常。此结果提示 ,Cariporide能明显减轻高脂饲料诱发的动脉粥样硬化 。

Aim To explore whether Na + H + exchanger (NHE) modulated atherogenesis, we investigated the effects of cariporide, a selective inhibitor of Na +- H + exchanger, against atherogenesis in animal models induced by high fat plus high cholesterol (high lipid) diet. Methods 22 healthy New Zealand rabbits were randomly divided into 3 groups: one group was fed normal chow (n=6), another group was fed high lipid diet chow served as atherogenesis control (n=8), the third group fed high lipid diet chow plus orally cariporide (0.1 mg/kg everyday) served as drug treated group (n=8). The blood was drawn from the central ear artery to assay serum lipoprotein at the prior experiment and animal sacrifice. Animals were killed in tenth week; the samples of arteries, lives and hearts were taken for morphologic analysis. Results The ultrastructures of aortic arteries showas follows. In normal diet group, the vascular intima were smooth and intact. In high lipid diet model group, the intima were become rough and thicker. A lot of lipoid foam cells migrated to regions of intima and smooth muscle cells (SMC) which associated injuries of internal elastic lamina. In the cariporide treated group, above described vascular injuries were significantly ameliorated, but it also was found that a few of foam cells scattered under intima of artery in a few cases (one rabbit). TC and low density lipoprotein cholesterol (LDLC) was significantly increased in both groups. Cariporide did not black increases of serum TC and LDLC levels. Conclusion Cariporide significantly decreased atherogenesis induced by hyperlipidemia. The actions of cariporide against atherogenesis were independent decreasing lipemia and mainly located in blood vessels and tissue.