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山东大学学报(医学版)

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非诺贝特对自发性高血压大鼠心肌重构及NF-κB表达的影响

李传保1,卜培莉1,张 运1,公茂磊2,侯晓阳1,郝明秀1,赵学强1,孟 晓1   

  1. 1. 教育部和卫生部心血管重构和功能研究重点实验室 山东大学齐鲁医院心内科,山东 济南 250012;2. 山东大学第二医院ICU, 山东 济南 250033
  • 收稿日期:2006-11-20 修回日期:1900-01-01 出版日期:2007-01-24 发布日期:2007-01-24
  • 通讯作者: 卜培莉

Effect of fenofibrate on myocardial remodeling and NF-κB expression in spontaneous hypertensive rats

LI Chuan-bao1,BU Pei-li1,ZHANG Yun1,GONG Mao-lei2,HOU Xiao-yang1,HOU Xiao-yang1,ZHAO Xue-qiang1,MENG Xiao1   

  1. 1. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health; Department of Cardiology, Qilu Hospital of Shandong University;2. Department of ICU, Second Hospital of Shandong University
  • Received:2006-11-20 Revised:1900-01-01 Online:2007-01-24 Published:2007-01-24
  • Contact: BU Pei-li

摘要: 探讨过氧化物酶体增殖物激活型受体α(peroxisome proliferator-activated receptor α,PPARα)激动剂非诺贝特对自发性高血压大鼠心肌组织核因子κB (nuclear factor kappa B, NF-κB)表达的影响及对心肌重构的干预作用。方法:将22只8周龄自发性高血压大鼠(SHR)随机分为SHR组(10只)及非诺贝特组(12只),同周龄Wistar-kyoto(WKY)大鼠10只作为正常对照。用药组给予非诺贝特60mg/(kg·d)灌胃8周。实验前后进行超声心动图检查,实验末处死动物进行组织学检查,实时定量逆转录-聚合酶链反应(RT-PCR)检测心肌NF-κB mRNA表达。结果:实验结束后,SHR组与WKY组相比室壁厚度、左室/体重比值显著增加(P<0.05),非诺贝特组与SHR组相比明显降低(P<0.05); SHR组与WKY组相比大鼠心肌NF-κB mRNA表达水平明显升高(P<0.05),非诺贝特组与SHR组相比明显降低(P<0.05);免疫组化显示,SHR组NF-κB在心肌组织分布广且呈强阳性表达,而非诺贝特组NF-κB着色弱,分布局限。结论:PPARα激动剂非诺贝特可通过抑制NF-κB表达来干预自发性高血压大鼠心肌重构的发生发展。

Abstract: Objective: To investigate the effect of fenofibrate on nuclear factor kappa B (NF-κB) in cardiac muscle and the preventive effect of fenofibrate on myocardial remodeling. Methods: Twenty-two spontaneous hypertensive rats (SHR) were randomly divided into two groups: a spontaneous hypertensive rat (SHR) group(n=10) and a fenofibrate group(n=12). A same age Wistar-kyoto(WKY) rat group(n=10) was selected as controls. The fenofibrate group was given drugs for 8 weeks. At the beginning and ending of the experiment, echocardiographic scanning was performed in each group. At the end of the experiment, the rats were executed and the cardiac muscle was examined histologically. Real-time RT-PCR was used to detect the mRNA expression of NF-κB. Results: At the end of the experiment, compared with the WKY group,the ventricular thickness and the ratio of left ventricle weight to body weight in the SHK group were significantly increased(P<0.05). Compared with the SHR group, the above parameters in the fenofibrate group were significantly decreased(P<0.05). The expression of cardiacal NF-κB mRNA in the SHR group was significantly higher than that in the WKY group(P<0.05), but showed a down regulation in the fenofibrate group(P<0.05). By immunohistochemistry, NF-κB staining in SHR group was strong and located at fargoing cardiac muscle tissues, but was weak and located within limits in fenofibrate group. Conclusion: The expression of NF-κB increases in cardiac muscle of SHR. Fenofibrate may delay the development of myocardial remodeling by decreasing the expression of NF-κB.

Key words: Ventricular remodeling, NF-κappa B, Fenofibrate, Rats, inbred SHR

中图分类号: 

  • R542.2
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