川陈皮素对脂毒性心肌病的保护作用机制研究  

Protective effect of Nobiletin on lipotoxic cardiomyopathy in rats

作　　者：车妍[1] 唐其柱[1] 张宁[1] 袁雨培 肖杨[1] Che Yan Tang Qizhu Zhang Ning Yuan Yupei Xiao Yang(Department of Cardiology, Cardiorascular Research Institude, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, Chin)

机构地区：[1]武汉大学人民医院心血管内科、武汉心血管病研究所、心血管病湖北省重点实验室,武汉430060

出　　处：《中华生物医学工程杂志》2016年第6期439-444,共6页Chinese Journal of Biomedical Engineering

基　　金：国家自然科学基金（81530012）

摘　　要：目的 探讨川陈皮素对高脂饮食诱导肥胖小鼠模型的心肌重构的保护作用及其抗纤维化的可能机制.方法 选用8-10周龄C57BL/6雄性小鼠38只,随机分为普通饮食（NC）组9只、普通饮食＋川陈皮素（NC＋Nob）组9只、高脂饮食（WD）组10只、高脂饮食＋川陈皮素（WD＋Nob）组10只,饲养24周后取材,称取小鼠的体重、脏脂及附睾脂肪重量,血流动力学检测评估心功能,麦胚凝集素（WGA）染色计算细胞横截面积,天狼猩红（PSR）染色评估纤维化程度,Western印迹法检测纤维化相关信号通路TGF-β1及其下游分子的表达变化.结果 与普通饮食组相比,高脂饮食组体重、脂肪重量、体重比胫骨长及心重比胫骨长明显升高（均P〈0.05）,血流动力学指标左心室舒张末期压力增加、舒张末容积减小、左心室收缩末期压力增加、心输出量减少、舒张持续时间延长、等容收缩期左室内压上升及下降最大速率减小（P〈0.05）,WGA染色显示心肌细胞横截面积增大（P〈0.05）,天狼猩红染色显示心肌细胞间质中纤维化水平提高（P〈0.05）,Western印迹发现致纤维化的TGF-β1通路激活.经川陈皮素治疗24周后,小鼠的体重、脏脂、附睾脂肪重量较高脂饮食组减轻,同时上述心功能指标改善,心肌细胞肥大减轻,间质纤维化水平下降,TGF-β1信号通路下调.结论 川陈皮素对高脂诱导的脂毒性心肌病具有改善心功能及抗纤维化作用,其抗纤维化机制可能通过抑制TGF-β1通路,继而下调smad2、smad3的磷酸化水平实现的.Objective To investigate the protective effect of Nobiletin （NOB） on myocardial remodeling in mice with high-fat diet-induced obesity,and its potential mechanism in anti-fibrosis. Methods Thirty-eight male C57BL/6 mice aged 8-10 weeks were randomly divided into the normal diet（NC）group（n=9）,NC＋NOB group（n=9）,high-fat diet（WD）group（n=10）,and WD＋NOB group（n=10）. All the rats were sacrificed after 24-week feeding,and the weights of body,hepatic fat and epididymal fat were measured. Hemodynamic study was used to evaluate the cardiac function. Wheat germ agglutinin （WGA） staining was used to calculate cell cross-sectional area. The level of fibrosis was assessed by picric sirius red （PSR）staining. The expression of transforming growth factor-β1（TGF-β1）and its downstream molecules in fibrosis-related signaling pathways were determined by Western blotting. Results Compared with the NC group,the body weight,fat weight,ratio of body weight to tibial length and ratio of heart weight to tibial length significantly increased in the WD group（all P〈0.05）. In the WD group,the hemodynamic indicators, the left ventricular end diastolic pressure,left ventricular end systolic pressureand diastolic duration increased,whereas the end diastolic volume,cardiac output and maximal rate of left ventricular pressure rise and fall in the isovolumic contraction phase decreased（P〈0.05）. WGA staining showed that the cross-sectional area of cardiomyocytes increased（P〈0.05）,and the PSR staining showed increased fibrosis in the myocardial interstitial cells（P〈0.05）. Western blotting found that the fibrotic TGF-β1 pathway was activated. At 24 weeks after the NOB treatment,the weights of body,hepatic fat and epididymal fat decreased compared with those in the WD group. Meanwhile,the cardiac function improved,the cardiomyocyte hypertrophy reduced,the level of interstitial fibrosis decreased,and the TGF-β1 signal pathway down-regulated. Conclusions NOB may improve the heart funct

关 键 词：肥胖症 纤维化 心室重构 川陈皮素 

分 类 号：R285.5[医药卫生—中药学]