氟伐他汀单用及与安体舒通联用对免颈动脉粥样硬化的影响  

The Effect of Fluvastatin Alone and Combined with Aldosterone on Carotid Atherosclerosis in Rabbits

作　　者：刘文华[1] 黄怀宇[1] 顾承志[1] 黄志东[1] 朱银圣 朱向阳[1] 刘春[3] 

机构地区：[1]南通大学第二附属医院神经内科,226001 [2]江苏省如皋市石庄中心医院,226531 [3]南通大学实验动物中心,226001

出　　处：《国际脑血管病杂志》2007年第3期177-180,共4页International Journal of Cerebrovascular Diseases

基　　金：江苏省卫生厅重点攻关课题（H200217）

摘　　要：　目的：探讨氟伐他汀单用及与醛固酮拮抗剂安体舒通联用对兔颈动脉粥样硬化的影响及其机制。方法：高脂饲养建立兔颈动脉硬化斑块模型。96只雄性新西兰兔分为对照组、高脂饮食组、氟伐他汀处理组（氟伐他汀组）以及氟伐他汀与安体舒通联合处理组（联合处理组），每组24只。用免疫组织化学法检测MMP-9表达，TONEL法检测细胞凋亡，HE染色观察颈动脉粥样硬化斑块结构变化。结果：（1）MMP-9在高脂饮食组表达水平高于对照组（P〈0．01），且8周、12周时高于4周时（P〈0．01）。氟伐他汀组12周时MMP-9表达低于4周时（P〈0．01）。联合处理组8周和12周时MMP-9表达低于4周时（P〈0．01）。氟伐他汀组和联合处理组MMP-9表达低于对照组和高脂饮食组（P〈0．01）。联合处理组8周和12周时MMP-9表达低于氟伐他汀组各对应时间点（P分别〈0．05和0．01）。（2）高脂饮食组TUNEL阳性细胞数多于对照组（P〈0．01），且8周、12周时多于4周时（P〈0．01）。氟伐他汀组和联合处理组8、12周时TUNEL阳性细胞数少于4周时（P〈0．01）。氟伐他汀组和联合处理组TUNEL阳性细胞数少于对照组、高脂饮食组各时间点（P〈0．01）；联合处理组8周和12周时TUNEL阳性细胞数少于氟伐他汀组（P〈0．01）。结论：随着高脂饲养时间的延长，动脉斑块中MMP-9表达增加，凋亡细胞数增多；他汀类药物可通过降低MMP-9表达和抑制细胞凋亡延缓动脉粥样硬化形成．联用醉固酮桔抗剂这一效应得到增强．Objective： To explore the effect of fluvastatin alone and combined with aldosterone antagonist （aldactone） on carotid atherosclerosis in rabbits and its mechanism. Methods： A rabbit carotid atherosclerosis model was established with high-lipid diet. Ninety-six male New Zealand rabbits were divided into 4 groups： control, high-lipid diet, fluvastatin alone, and fluvastatin combined with aldosterone （n = 24 in each group）. Matrix metalloproteinase-9 （MMP-9） expression was detected by immunohistochemistry, the apoptosis was detected by TUNEL, and the structural changes in carotid atherosclerotic plaque were observed by hemotoxylin and eosin （HE） staining. Results： MMP-9 expression in the high-lipid diet group was higher than that in the control group （P 〈 0.01 ）, and it was higher at 8 and 12 weeks than that at 4 weeks （P 〈 0.01）; MMP-9 expression at 12 weeks was lower than that at 4 weeks in the fltwastatin alone group （P 〈0.01）; MMP-9 expression at 8 and 12 weeks in the combined group was lower than that at 4 weeks （P 〈0. 01）; MMP-9 expression in both fluvastatin and combined groups was lower than that in the control and high-lipid diet groups （P 〈0.01）; and MMP-9 expression at 8 and 12 weeks in the combined group was lower than that in the fluvastatin group at each corresponding time point （P 〈 0.05 and 0.01, respectively）, The numbers of TUNEL positive cells in the high-lipid diet group were higher than those in the control group （P 〈 0.01 ）, and they were higher at 8 and 12 weeks than those at 4 weeks （P 〈 0.01 ）; The numbers of TUNEL positive cells at 8 and 12 weeks in the fluvastatin alone and combined groups were lower than those at 4 weeks （P 〈0.01）; the numbers of TUNEL positive cells in the fluvastatin alone and combined groups were lower than those in the control and high-lipid groups in each time point （P 〈 0.01 ）; and the numbers of TUNEL positive cells at 8 and 12 weeks in the combined group was lower than those in the

关 键 词：颈动脉粥样硬化 基质金属蛋白酶-9 氟伐他汀 安体舒通 

分 类 号：R54[医药卫生—心血管疾病]