上海交通大学学报（医学版）

›› 2009, Vol. 29 ›› Issue (9): 1026-.

• 论著（基础研究） • 上一篇    下一篇

法舒地尔对ApoE-/-小鼠动脉粥样硬化斑块的影响

武多娇, 纪 艳, 吴永杰, 高平进, 张 怡, 朱鼎良   

  1. 上海交通大学 医学院瑞金医院 上海市高血压研究所 上海市血管生物学重点实验室, 上海 200025
  • 出版日期:2009-09-25 发布日期:2009-09-29
  • 通讯作者: 朱鼎良, 电子信箱: zhudingliang@sibs.ac.cn。
  • 作者简介:武多娇（1979—）, 女, 博士生；电子信箱: wuduojiao@126.com。
  • 基金资助:

    国家重点基础研究发展计划（“973”计划）（2004CB518603）和上海市科委基金（08JC1417400, 08DZ2200400，08410701900）

Anti-atherogenic effects and mechanism of fasudil on ApoE-/- mice

WU Duo-jiao, JI Yan, WU Yong-jie, GAO Ping-jin, ZHANG Yi, ZHU Ding-liang   

  1. Shanghai Key Laboratory of Vascular Biology, Shanghai Institute of Hypertension, Ruijin Hospital|School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2009-09-25 Published:2009-09-29
  • Supported by:

    National Basic Research Program of China，“973”Program，2004CB518603；Shanghai Science and Technology Committee Foundation, 08JC1417400, 08DZ2200400，08410701900

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摘要：

目的 观察特异性Rho激酶抑制剂法舒地尔对载脂蛋白E基因敲除（ApoE-/-）小鼠动脉粥样硬化斑块进展的影响，并探讨其可能的作用机制。方法 8周龄ApoE-/-小鼠高脂饲料喂养12周后给予法舒地尔干预，12周后结束实验。将ApoE-/-小鼠随机分为三组（n=10）：对照组（饮用水）、法舒地尔低剂量组（30 mg•kg-1•d-1）和法舒地尔高剂量组（100 mg•kg-1•d-1）。在实验结束时，测量小鼠体质量、血压及血脂水平；对头臂干动脉粥样硬化病变进行病理学检查；化学发光法及组织荧光法检测小鼠胸主动脉超氧阴离子和活性氧（ROS）。结果 法舒地尔干预对ApoE-/-小鼠体质量、收缩压及血脂水平均无明显影响。与对照组相比，法舒地尔高剂量组头臂干动脉粥样硬化斑块面积和动脉内—中膜厚度（IMT）分别减少54%（P<0.01）和42%（P<0.05）。法舒地尔干预使ApoE-/-小鼠胸主动脉原位ROS的生成较对照组明显减少（P<0.01）；法舒地尔高剂量组胸主动脉的超氧阴离子产量低于对照组（P<0.05）。结论 阻断Rho激酶可抑制ApoE-/-小鼠头臂干动脉粥样硬化斑块的进展，其作用独立于血压和血脂水平，可能与抗氧化应激有关。

关键词: 法舒地尔, 动脉粥样硬化, 氧化应激, 小鼠

Abstract:

Objective To examine the effects of fasudil, a specific Rho kinase inhibitor, on atherosclerotic plaque progression in apolipoprotein E-deficient (ApoE-/-) mice, and explore the potential mechanisms. Methods After 12 weeks of fat-feeding, ApoE-/- mice were orally administrated with fasudil for 12 weeks. Mice were randomly allocated into three groups: control group (tap water), low-dose fasudil group (30 mg•kg-1•d-1) and high-dose fasudil group (100 mg•kg-1•d-1) (n=10 in each group). At the end of the study, body weight, blood pressure and blood lipid were measured, and atherosclerosis of brachiocephalic arteries were determined by histological examinations. Production of superoxide anion and reactive oxygen species (ROS) were measured in the thoracic aorta of mice using chemiluminescence and histofluorescence techniques. Results Fasudil treatment had no effect on body weight, blood pressure and blood lipid concentrations of ApoE-/- mice. The plaque area and intima-medial thickness of brachiocephalic artery were attenuated by 54% and 42%, respectively in high-dose fasudil group in comparison with control group (P<0.01 and P<0.05, respectively). Furthermore, fasudil treatment significantly reduced in situ ROS production of thoracic aorta (P<0.01). And the production of superoxide anion in the aortic wall was lower in high-dose fasudil group than in control group（P<0.05）. Conclusion Blocking Rho kinase may inhibit the progression of atherosclerotic plaques of brachiocephalic arteries in ApoE-/- mice, and the effect may be independent of blood pressure and blood lipid changes, while probably be related with the anti-oxidative stress effect.

Key words: fasudil, atherosclerosis, oxidative stress, mice