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|本期目录/Table of Contents|

阿托伐他汀对高同型半胱氨酸血症诱发动脉粥样硬化的干预作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第1期
页码:
1-006
栏目:
基础研究
出版日期:
2014-09-25

文章信息/Info

Title:
Protective effects of atorvastatin against hyperhomocysteinemia-induced atherosclerosis
作者:
鲍晓梅; 郑宏超
(上海市徐汇区中心医院心内科，上海 200031)
Author(s):
BAO Xiao-mei;  ZHENG Hong-chao
(Department of Cardiology, Central Hospital, Shanghai Xuhui District, Shanghai 200031, China)
关键词:
高同型半胱氨酸血症; 动脉粥样硬化; 阿托伐他汀;  凋亡; 活性氧; NADPH氧化酶
Keywords:
hyperhomocysteinemia;  atherosclerosis;  atorvastatin;  apoptosis;  oxidative stress;  NADPH oxidase
分类号:
R972
DOI:
-
文献标识码:
A
摘要:
目的:观察阿托伐他汀对动脉粥样硬化斑块的影响, 并对其作用机制进行初步探讨。方法： 20 g/L L-蛋氨酸灌胃法建立ApoE基因敲除小鼠高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)模型，按实验分组, 给予不同剂量阿托伐他汀治疗1个月后，用高效液相色谱荧光法测定血浆同型半胱氨酸(Hcy)水平，相差显微镜下观察小鼠主动脉根部病理学形态，免疫组织化学法检测主动脉血管平滑肌SM-α-actin的表达，TUNEL法检测小鼠主动脉斑块中的细胞凋亡指数，NBT及光泽精化学发光法检测血管局部活性氧(reactive oxygen species,ROS)水平, 光泽精化学发光法检测主动脉血管NADPH氧化酶(NADPH oxidase,Nox)活性，Western印迹法检测Nox4蛋白表达。结果： ApoE-/-小鼠蛋氨酸喂养3个月后，血浆Hcy水平升高，AS斑块形成。阿托伐他汀治疗1个月后，呈剂量依赖性地降低小鼠血浆Hcy水平，延缓AS病变的进程，减少斑块内凋亡细胞数量，降低了血管壁局部ROS水平，Nox活性及Nox4蛋白表达（均P<0.05）。结论： 阿托伐他汀治疗后，HHcy ApoE-/-小鼠AS病变进程延缓，其作用机制与其下调Nox4来源的ROS水平、抑制血管内皮细胞凋亡有关。
Abstract:
AIM:To study the protective effects of atorvastatin on hyperhomocysteinemia (HHcy)-induced atherosclerosis and possible mechanisms. METHODS: Seven-week-old male ApoE-/- mice were fed with 20 g/L L-methionine for 3 months to establish an atherosclerosis plaque model with HHcy. In the divided groups (without or with atorvastatin pretreatment for 1 month), plasma Hcy levels were measured by high-performance liquid chromatography. Aortic roots were isolated for morphologic pathology and immunohistochemistry and TUNEL analysis were conducted to investigate the apoptosis index in the lesion. Aortic ROS production was measured by nitroblue tetrazolium (NBT) formazan and lucigenin-enhanced chemiluminescence, aortic NADPH oxidase activity was evaluated with lucigenin-enhanced chemiluminescence, and NADPH oxidase 4 (Nox4) was evaluated with Western blot. RESULTS: Three-month high methionine diet induced the formation of atherosclerosis plaque in the aorta of ApoE-/- mice accompanied by an increase of Hcy in plasma. Administration of atorvastatin for 1 month reduced plasma Hcy level, suppressed development of atherosclerosis plaque, inhibited apoptosis in atherosclerosis plaque and NBT formazan deposit, and decreased ROS formation, NADPH oxidase activation and Nox4 expression in the vessel wall. CONCLUSION: Atorvastatin attenuates HHcy-induced atherosclerosis in ApoE-/- mice. Its mechanism may be related to the inhibition of Nox4-derived oxidative stress and the subsequent decrease of apoptosis of endothelial cells.

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备注/Memo

备注/Memo:
收稿日期：2014-04-30.
基金项目：上海市自然科学基金项目资助（12ZR1429100）
作者简介：鲍晓梅,副主任医师，博士Email:baoxiaomei_nt@sina.cn
更新日期/Last Update: 2015-01-20