血浆同型半胱氨酸水平升高促进小鼠动脉粥样硬化的研究  

Hyperhomocysteinemia promotes atherosclerosis in apolipoprotein E-deficient mice

作　　者：王仁庆[1] 王意琴 李伟煊[1] 张选红[1] 李红宇[1] 谭红梅[1] 

机构地区：[1]中山大学中山医学院病理生理学教研室,广东广州510080

出　　处：《解剖学研究》2016年第3期161-164,共4页Anatomy Research

基　　金：国家自然科学基金(81370371;81570394);广东省自然科学基金(2014A030313066)

摘　　要：目的本研究通过喂饲高蛋氨酸合并高脂饲料使小鼠血浆Hcy水平升高,同时诱发动脉粥样硬化病变,观察血浆同型半胱氨酸水平升高对动脉粥样硬化发生的促进作用。方法载脂蛋白E基因敲除(apo E-/-)小鼠随机分为对照组、高脂饮食组及高脂合并高蛋氨酸饮食组。高脂饮食组及高脂合并高蛋氨酸饮食组小鼠从第8周开始连续喂食相应的饲料10周,对照组喂饲普通饲料。实验结束时静脉取血离心后,取血浆检测同型半胱氨酸水平;同时取心脏上半部分连同主动脉根部5 mm,OCT冰冻切片包埋胶包埋后,切取主动脉瓣膜的冰冻切片并进行油红染色、正置显微镜连接数码相机照相后,采用Image Plus软件定量分析斑块的面积。将胸、腹主动脉(主动脉根部至肾动脉分叉处)分离干净、剪下并沿长轴剪开,进行苏丹Ⅵ染色、照相后,体视显微镜连接数码相机照相后,采用Image Plus软件定量分析斑块的面积、整个血管面积及病变所占比例。结果高脂合并高蛋氨酸饮食组血浆同型半胱氨酸水平显著高于对照组和高脂饮食组。高脂饮食组及高脂合并高蛋氨酸饮食组主动脉瓣膜及胸腹主动脉斑块面积均显著高于对照组,且高脂合并高蛋氨酸饮食组斑块面积显著高于高脂饮食组,表明该组动脉粥样硬化程度较更高脂饮食组更严重。结论高脂饮食可诱发动脉粥样硬化。高蛋氨酸饮食可导致血浆同型半胱氨酸水平升高,并进一步促进动脉粥样硬化的发生。Objective HHcy was induced by feeding high fat plus high methionine diet, the effect of hyperhomocystein- emia （HHcy） on atherosclerosis in apolipoprotein E-deficient （apoE^-/-） mice was investigated. Methods ApoE^-/- mice were randomly divided into the control group, the high fat diet group and the high fat plus high methionine diet group. Mice were fed a control rodent diet, or a high fat diet, or a high fat plus high methionine diet at 8 weeks of age. After 10 weeks on the respective diets, mouse plasma was collected for homocysteine （Hcy） measurements. The hearts and proximal aorta were excised and embedded in optimal cutting temperature compound. Section the heart from the apex arch. Discard the lower half of the heart. Cut the heart till the begin- ning of the aortic sinus. Start to collect 6-μm-thick cryosections when the aortic valves appeared. Sections were stained with oil red O and hematoxylin, and the lesion areas were counted using the Image Plus program. Aortas were removed from the heart and excised from the aortic arch to just beyond the renal artery, cut longitudinally, pinned onto a silicon dish, and stained with saturated Sudan IV in propylene glycol. Total area and atherosclerotic lesion area of the whole aorta were measured using the Image Plus program. Results The plasma hcy level of high fat plus high methionine diet group is significantly higher than these of the control and the high fat diet groups. The atherosclerotic lesions in the aortic valves and the whole aorta of high fat diet group were significantly larger than that of the control group. The atherosclerotie lesions in the aortic valves and the whole aorta of high fat plus high methi- onine diet group were significantly larger than these of the control and the high fat diet groups. Conclusion High fat diet can induce atherosclerosis. High fat plus high methionine diet can increase plasma Hcy level, thus further promote atherosclerosis.

关 键 词：动脉粥样硬化 同型半胱氨酸 高蛋氨酸饮食 高脂饮食 

分 类 号：R543.5[医药卫生—心血管疾病]