下调心肌CD36的表达对肥胖小鼠心肌活性氧簇生成的影响
投稿时间:2016-01-19  修订日期:2016-01-25  点此下载全文
引用本文:张逸杰,刘景,戴明彦,曹权,何文博,包明威.下调心肌CD36的表达对肥胖小鼠心肌活性氧簇生成的影响[J].医学研究杂志,2016,45(8):46-51
DOI: 10.11969/j.issn.1673-548X.2016.08.013
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作者单位E-mail
张逸杰 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
刘景 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
戴明彦 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
曹权 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
何文博 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
包明威 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室 mbao@whu.edu.cn 
基金项目:国家自然科学基金资助项目(面上项目)(81570460);国家自然科学基金青年科学基金资助项目(81500668);中央高校基本科研业务费专项资金资助项目(2042014kf0172)
中文摘要:目的 研究定向下调心肌CD36的表达对高脂饮食诱导的肥胖小鼠心肌组织中活性氧簇(ROS)含量的影响。方法 4周龄的雄性C57小鼠,随机分为正常对照组(N-mock)、肥胖对照组(O-mock)及肥胖干预组(O-CD36),采用高脂饮食诱导肥胖。6周龄时,向心肌内分别注射靶向CD36(O-CD36)或靶向无关基因(N-mock、O-mock)的重组慢病毒。10周后,取小鼠心室组织检测CD36的mRNA及蛋白表达水平;行油红O染色检测心肌组织内中性脂质含量;并使用冷冻切片染色法及流式细胞术检测心肌细胞内ROS含量。结果 慢病毒介导的RNA干扰显著下调了O-CD36小鼠心肌组织中CD36的表达。肥胖引起心肌组织内中性脂质蓄积,下调心肌CD36的表达显著减少了中性脂质的含量。高脂饮食还导致心肌ROS的含量显著增加,而下调CD36的表达可以改善甚至逆转这一进程。结论 CD36在高脂肪酸代谢所引起的ROS生成增加中起重要作用,定向下调心肌CD36的表达可以减少心肌组织ROS的含量,改善心肌氧化应激。
中文关键词:RNA干扰  CD36  肥胖模型  中性脂质  活性氧簇
 
Effects of Cardiac CD36 Inhibition on Generation of Myocardial Reactive Oxygen Species
Abstract:Objective To study the effects of cardiac-specific CD36 inhibition on generation of myocardial reactive oxygen species (ROS). Methods Four-week-old male C57 mice were randomized into normal control group (N-mock), obese control group (O-mock) and obese intervention group (O-CD36). High-fat-diet (HFD) was used to induce obesity in this study. Mice were subjected to intramyocardial injection with recombinant lentiviral vectors carrying short hairpin RNAs targeting murine CD36 (for O-CD36) or irrelevant gene (for N-mock and O-mock). Ten weeks later, ventricular tissues were obtained. CD36 mRNA and protein expression were measured by RT-PCR and Western blot. Myocardial neutral lipid content was detected by oil red O staining. Two methods were chosen to measure the ROS production in the myocardium. Results Lentivirus-mediated RNAi effectively down-regulated CD36 expression in O-CD36 mice heart. HFD induced obesity increased neutral lipid deposition in the heart, but this process was ameliorated by cardiac CD36 inhibition. HFD feeding induced myocardial ROS overproduction, which was reversed by cardiac-specific CD36 suppression. Conclusion CD36 plays an important role in myocardial ROS overproduction during fatty acid hypermetabolic states. Targeted cardiac CD36 inhibition improves myocardial ROS generation, and ameliorates myocardial oxidative stess as well.
keywords:RNA interference  CD36  Obese models  Neutral lipids  Reactive oxygen species
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