罗格列酮、辛伐他汀合用对兔动脉粥样硬化形成的影响

目的探讨罗格列酮、辛伐他汀合用对兔动脉粥样硬化（AS）形成的影响及可能的作用机制。方法40只日本大耳白兔随机分为五组,每组8只。正常对照组：普通颗粒饲料喂饲11周。高脂模型组：高脂饲料（1％胆固醇＋8％猪油＋普通颗粒饲料）喂饲11周。罗格列酮组：高脂饲料喂饲同时口服罗格列酮0．5mg·kg^-1·d^-1。辛伐他汀组：高脂饲料喂饲同时口服辛伐他汀2．5mg·kg^-1·d^-1。联合用药组：高脂饲料喂饲同时口服罗格列酮0．5mg·kg^-1·d^-1和辛伐他汀2．5mg·kg^-1·d^-1.12周末实验结束后获取血浆和主动脉全长标本进行生化和病理分析。结果各用药组与高脂模型组比较C-反应蛋白（CRP）、内皮素（ET）浓度明显降低,以联合用药组降低最明显（P〈0．01）;一氧化氮（NO）水平升高,以联合用药组升高最显著（P〈0．01）。罗格列酮组、联合用药组与高脂模型组比较,血浆非对称二甲基精氨酸（ADMA）水平下降（P〈0．01）。辛伐他汀组、联合用药组与高脂模型组比较,血浆总胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL—C）明显降低,高密度脂蛋白胆固醇（HDL-C）水平明显升高（P〈0．01）。高脂模型组、各用药组主动脉内膜有不同程度的脂质斑块形成,内膜增厚程度不同,高脂模型组脂质斑块最多,内膜／中膜厚度比值90．17±23．03用药组斑块明显减少,以联合用药组脂质斑块最少,内膜／中膜厚度比值最小13．56±0．72（P〈0．01）。结论罗格列酮、辛伐他汀通过抑制炎症反应,改善内皮功能、调脂等各自不同途径抑制动脉硬化的形成,联合应用具有协同作用。

The Effect of Rosiglitazone and Simvastatin on Atherosclerosis in Cholesterol-fed Rabbits

Objective To study the effect of Rosiglitazone and Simvastatin on atherosclerosis and potential mechalism in rabbits. Methods 40 healthy Japanese big-ear rabbits were randomly divided into five groups with 8 rabbits in each group. Normal control group was fed with common forage for 11 weeks. Model group was fed with fat forage （ common forage contained 1% cholesterol and 8% lard）. Rosiglitazone group was fed with fat forage and rosglitazone 0.5 kg^-1.d^-1. Simvastatin group was fed with fat forage and samvastatin 2.5 kg^-1. d^-1. Rosiglitazone and Simvastatin groups were fed with fat forage and rosglitazone 0.5 kg^-1.d^-1. and samvastatin 2.5 kg^-1. d^-1. At the end of the experiment, blood samples of the rabbits were collected for biochemistry analysis and aorta was prepared for morphologic analysis. Results Compared with the control group, the levels of serum TC, TG, LDL-C, CRP, ET-1 and ADMA in model group increased obviously and the levels of NO and HDL-C decreased（P 〈0.01）. The levels of serum CRP, ET-1 in the treatment groups were significantly lower and the levels of NO were higher than those of normal group（P 〈 0.01）. Compared with those in model group, the levels of serum ADMA in haplo- Rosiglitazone group or in the combination group significantly decreased（P 〈 0.01）. The levels of TC, TG and LDL-C in haplo-Simvastation group or in the combination group were significantly lower than those of the model group（ P 〈 0.01）. The atheromatous plaques area and intima-to-media in model group were obviously higher than those of the normal group（ P 〈 0.01）. The combinationgroup significantly reduced the extent of atherosclerosis of longitudinal section. Conclusion Rosiglitazone and Samvastatin can prevent the development of atherosclerosis through inhibitting the inflammatory reaction, effect, protecting endothelial function and regulatting lipid metabolism. They have synergetic effect.