辛伐他汀和氨氯地平对实验性兔动脉粥样硬化进程中HO／CO系统的影响

Effects of simvastatin and amiodipine on heme oxygenase/carbon monoxide system in atherosclerosis model of rabbit

目的探讨血红素加氧酶．一氧化碳系统在动脉粥样硬化中的变化、相互关系及辛伐他汀、氨氯地平对动脉粥样硬化进程中血红素加氧酶-一氧化碳的影响。方法家兔予以高胆固醇饮食（n=24）18周，8周后改用普通饮食并随机分为三组，模型组停用高胆固醇饮食，改普通饮食（n=8）；辛伐他汀组给予喂饲辛伐他汀进行药物干预8周，氨氯地平组给予喂饲氨氯地平进行药物干预8周（n=8）。同时设正常对照组（n=8）：给予普通饲料喂养16周。然后取静脉血分别用Chalmers A．H、硝酸还原酶法测定各实验组血中CO，取主动脉组织用免疫组织化学方法测定主动脉组织中HO-1的表达；并比较组间各项参数的差异。结果16周末模型组血脂水平、血浆一氧化碳水平、血红素加氧酶-1表达较对照组明显升高。辛伐他汀组血浆TC、TG、LDL下降明显，HDL升高；血浆一氧化碳水平及血红素加氧酶-1表达均明显降低。而氨氯地平组血脂无明显变化；血浆一氧化碳水平、血红素加氧酶-1表达亦明显降低。结论动脉粥样硬化进程中，辛伐他汀、氨氯地平均可以通过下调血红素加氧酶／一氧化碳系统而延缓动脉粥样硬化进程。

Objective To investigate the change rule and correlation of heme oxygenase-1 （HO-1） / carbon monoxide（CO） and the influence of simvastatin and amlodipine in atherosclerotic progress. Methods The rabbits received 1% cholesterol diet （ n = 24） for eight weeks. After eight weeks, rabbits were fed with normal diet for eight weeks. The rabbits in model group （ n = 8） were administrated with cholesterol diet. The rabbits in simvastatin group （ n = 8） were,administrated with simvastatin. The rabbits in amlodipine group （ n = 8） were administrated with amlodipine. The levels of serum lipids and plasma carbon monoxide were obtained at the beginning, the 8th week and the 16th week. The expression of heme oxygenase-1 in the thoracia aortic tissue were observed with immunohistochemistry technique. Results By the end of 16th week, the levels of serum lipids and plasma carbon monoxide in model group were obviously increased, however, the expression of heme oxygenase-1 were markedly decreased. Compared with model group, the levels serum lipids and plasma carbon monoxide in simvastatin group were significantly decreased, while the expression of heine oxygenase - 1 in aortic great reduced. The levels serum lipids in amlodipine group were not significant changed, the levels of plasma carbon monoxide were obviously decreased, while the expression of beme oxygenase-1 in aortic great reduced. Conclusions In atherosclerotic progress, heme oxygenase-1 （ HO-1 ） / carbon monoxide（CO） appeared the reciprocal relationship, and amlodipine may suppress atherosclerotie progress by decreasing the system.