吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (02): 240-244.doi: 10.13481/j.1671-587x.20160210

• 基础研究 • 上一篇    下一篇

瑞舒伐他汀对载脂蛋白E基因敲除小鼠动脉粥样硬化的治疗作用及其机制

吕文轩1, 李文耀1, 范思佳1, 赵殊2, 郭五虎3, 陈丽娟1, 邓悦4   

  1. 1. 吉林大学第二医院心血管内科, 吉林长春 130041;
    2. 吉林省白山市通化矿业集团总医院心内科, 吉林白山 134300;
    3. 内蒙古自治区兴安盟科右中旗高力板镇义和道卜卫生院, 内蒙古兴安盟 029408;
    4. 长春中医药大学附属医院心内科, 吉林长春 130021
  • 收稿日期:2015-12-09 发布日期:2016-03-31
  • 通讯作者: 陈丽娟,教授,硕士研究生导师(Tel:0431-88796625,E-mail:1009579793@qq.com);邓悦,教授,博士研究生导师(Tel:0431-86177913,E-mail:18443154122@163.com) E-mail:1009579793@qq.com;18443154122@163.com
  • 作者简介:吕文轩(1990-),男,山东省聊城市人,在读医学硕士,主要从事心血管疾病基础和临床方面的研究。
  • 基金资助:

    国家中医药管理局国家中医临床研究基地业务建设科研专项基金资助课题(JDZX2012073)

Therapeutic effect of rosuvastatin on atherosclerosis of apolipoprotein E(ApoE)-knockout mice and its mechanism

LYU Wenxuan1, LI Wenyao1, FAN Sijia1, ZHAO Shu2, GUO Wuhu3, CHEN Lijuan1, DENG Yue4   

  1. 1. Department of Cardiology, Second Hospital, Jilin University, Changchun 130041, China;
    2. Department of Cardiology, General Hospital, Tonghua Mining Group, Baishan City, Jilin Province, Baishan 134300, China;
    3. Yihedaobu Health Center in Gaoliban Town, Keyouzhong Banner, Hinggan League, Inner Mongolia Autonomous Region, Hinggan League 029408, China;
    4. Department of Cardiology, Affiliated Hospital, Changchun University of Traditional Chinese Medicine, Changchun 130021, China
  • Received:2015-12-09 Published:2016-03-31

摘要:

目的: 探讨瑞舒伐他汀对载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化模型血脂水平、动脉粥样硬化斑块及斑块内细胞凋亡的影响,阐明瑞舒伐他汀抑制动脉粥样斑块进展及斑块内细胞凋亡的机制。方法: 选取健康6周龄雄性ApoE-/-小鼠30只,随机分为高脂饮食组、高脂+他汀组和普通饮食对照组,每组10只。前2组小鼠给予高脂饮食,普通饮食对照组小鼠给予普通饲料,喂养4周后,3组小鼠分别给予0.9%生理盐水、瑞舒伐他汀(10mg·kg-1·d-1)和0.9%生理盐水灌胃8周,ELISA法检测各组小鼠血清血脂水平,HE染色观察小鼠动脉粥样硬化斑块大小,TUNEL法检测斑块内细胞凋亡,免疫组织化学染色法检测凋亡相关基因Bax蛋白表达。结果: 高脂+他汀组小鼠血清总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平明显低于高脂饮食组(P<0.05或P<0.01),高脂+他汀组高密度脂蛋白胆固醇(HDL-C)水平明显高于高脂饮食组(P<0.01)。高脂饮食组小鼠主动脉粥样斑块呈巨块型,斑块内可见大量泡沫细胞、胆固醇结晶、坏死细胞及炎性细胞;高脂+他汀组小鼠主动脉粥样斑块较小,泡沫细胞、坏死细胞和炎性细胞均较少;高脂+他汀组小鼠主动脉粥样斑块面积明显小于高脂饮食组(P<0.01);高脂+他汀组小鼠主动脉粥样斑块内细胞凋亡指数明显低于高脂饮食组(P<0.01)。与高脂饮食组比较,高脂+他汀组小鼠Bax蛋白表达明显降低。结论: 瑞舒伐他汀可以抑制动脉粥样斑块进展,抑制斑块内细胞凋亡,其作用机制可能与线粒体途径有关。

关键词: 瑞舒伐他汀, 主动脉粥样硬化, 细胞凋亡, Bax

Abstract:

Objective: To explore the influence of rosuvastatin in the lipid levels, atherosclerosis plaque and apoptosis in the plaque of atherosclerotic apolipoprotein E(ApoE)-knockout mouse models, and to clarify the mechanism of rosuvastatin in inhibiting atheromatous plaque and apoptosis in the plaque.Methods: Thirty healthy six-week old male mice were randomly divided into high fat diet group(n=10), rosuvastatin group(n=10) and general diet control group(n=10).The mice in first two groups were fed with high fat diet, and the mice in general diet control group were fed with general diet;4 weeks later the mice in three groups were respectively given 0.9% NaCl solution, rosuvastatin(10 mg·kg·d-1) and 0.9% NaCl solution by gavage for 8 weeks.And then ELISA was used to detect the serum lipid levels, the area of atherosclerotic plaque was measured by HE staining, and the apoptosis in plaques was detected by TUNEL method;the expression of apoptosis-assoicated gene Bax protein was measured by immunohistochemical staining.Results: Compared with high fat diet group, the levels of total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) of the mice in rosuvastatin group were significantly decreased(P<0.05 or P<0.01), and the 1evel of high density lipoprotein cholesterol(HDL-C) was significantly increased(P<0.01).The aortic atherosclerotic plaque of the mice in high fat diet group was massive with a great quantity of foam cells, cholesterol crystal, necrotic cells and inflammatory cells in the plaque;the aortic atherosclerotic plaque of the mice in rosuvastatin group was smaller with less foam cells, necrotic cells and inflammatory cells; the aortic atherosclerotic plaque area of the mice in rosuvastatin group was significantly smaller than that in high fat diet group(P<0.01);the apoptotic index in the aortic atherosclerotic plaque of the mice in rosuvastatin group was significantly lower than that in high fat diet group(P<0.01).Compared with high fat diet group, the expression of Bax protein in rosuvastatin group was significantly decreased.Conclusion: Rosuvastatin may inhibit the progression of atherosclerotic plaque and the apoptosis in plaques through mitochondrial pathway.

Key words: rosuvastatin, aortic atherosclerosis, apoptosis, Bax

中图分类号: 

  • R972