心阴片对慢性心力衰竭模型小鼠线粒体能量代谢的影响  

Effects of Xinyin Tablets(心阴片)on Mitochondrial Energy Metabolism in Chronic Heart Failure Model Mice

作　　者：刘惠 王陵军[1,2] 王俊岩[1,2] 冼绍祥 方红城[3] 叶桃春 LIU Hui;WANG Lingjun;WANG Junyan;XIAN Shaoxiang;FANG Hongcheng;YE Taochun(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,510405;Lingnan Medical Research Center of Guangzhou University of Chinese Medicine;Shenzhen Hospital of Integrated Chinese and Western Medicine)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]广州中医药大学岭南医学研究中心 [3]深圳中西医结合医院

出　　处：《中医杂志》2021年第12期1073-1079,共7页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81973777);广州中医药大学第一附属医院青年科研基金(211010010116);广东省省级科技计划(2018B020207009);第六批全国老中医药专家学术经验继承项目;广州市科技计划(202102080228)。

摘　　要：目的探讨心阴片治疗慢性心力衰竭的可能作用机制。方法60只C57BL/6J小鼠随机分为假手术组8只,模型组、曲美他嗪组及心阴片低、高剂量组各13只。除假手术组外,其余各组采用主动脉弓缩窄术制备慢性心力衰竭模型。造模后心阴片低剂量组给予心阴片292.5mg/kg灌胃,心阴片高剂量组给予心阴片1170mg/kg灌胃,曲美他嗪组给予盐酸曲美他嗪片15mg/kg灌胃,假手术组和模型组给予0.1ml/10g蒸馏水灌胃。各组均每天1次,共8周。检测心功能各指标包括左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左室舒张内径(LVIDd)、左室收缩内径(LVIDs),观察心脏组织形态学、心肌组织胶原纤维沉积、心肌细胞线粒体超微结构变化,检测心脏组织过氧化物酶体增殖物活化受体γ协同活化因子1α(PGC-1α)、核呼吸因子1(NRF1)、线粒体转录特异因子B2(TFB2M)蛋白表达及心肌组织三磷酸腺苷(ATP)水平。结果与假手术组比较,模型组LVEF、LVFS明显下降,LVIDd、LVIDs明显升高,PGC-1α、NRF1及TFB2M蛋白表达显著降低,心脏组织ATP水平降低(P<0.05);心肌细胞明显增大,排列不规则,胶原纤维沉积明显增多,线粒体数量减少、体积肿胀,线粒体膜结构不完整,嵴模糊。与模型组比较,曲美他嗪组及心阴片低、高剂量组LVEF、LVFS、LVIDs改善,ATP水平显著提高(P<0.05);心阴片低剂量组PGC-1α、TFB2M蛋白表达,心阴片高剂量组PGC-1α、NRF1、TFB2M蛋白表达,曲美他嗪组NRF1、TFB2M蛋白表达均明显升高(P<0.05);各组心脏组织形态学明显改善,胶原纤维沉积明显减轻,线粒体超微结构破坏较少。结论心阴片能改善慢性心力衰竭模型小鼠心功能,其机制可能是调控PGC-1α/NRF1/TFB2M信号通路进而改善线粒体能量代谢。Objective To explore the possible mechanism of Xinyin Tablets(心阴片)in treating chronic heart failure(CHF).Methods Sixty C57 BL/6 J mice were randomized into sham operation group(n=8),model group(n=13),trimetazidine group(n=13)and Xinyin Tablets low dose(n=13)and high dose(n=13)groups.Aortic arch constriction was carried out to prepare the model of CHF in all groups except for the sham operation group.After modeling,mice in the Xinyin Tablets low dose group and high dose group were given 292.5 mg/kg and 1170 mg/kg Xinyin Tablets by gavage,respectively;15 mg/kg trimetazidine and 0.1 ml/10 g distilled water were administered by gavage in trimetazidine group and sham operation group,respectively;the interventions in all the groups were given to the mice once daily for eight weeks.Cardiac function indicators including left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),left ventricular internal dimension diastole(LVIDd)and left ventricular internal dimension systole(LVIDs)were measured;the cardiac tissue morphology,the cardiac tissue collagen fiber deposition and the changes of myocardial cell mitochondrial ultrastructure were assessed;the protein expression of peroxisome proliferator-activated receptorγco-activator 1α(PGC-1α),nuclear respiration factor 1(NRF1),and mitochondrial transcription factor B2(TFB2 M)in the cardiac tissues,as well as the myocardial tissue adenosine triphosphate(ATP)level were detected.Results Compared to the sham operation group,the model group had significantly lower levels of LVEF and LVFS,higher levels of LVIDd and LVIDs,decreased expression of PGC-1α,NRF1 and TFB2 M proteins,and decreased level of ATP in cardiac tissue(P<0.05);the myocardial cells were significantly increased with irregular arrangement;the deposition of collagen fibers obviously increased;the number of mitochondria significantly decreased with swollen volume;the mitochondrial membrane structure was incomplete,and the cristae was blurred.Compared to those of the model group,t

关 键 词：慢性心力衰竭 线粒体 能量代谢 心阴片 过氧化物酶体增殖物活化受体γ协同活化因子1α 核呼吸因子1 线粒体转录特异因子B2 

分 类 号：R541.6[医药卫生—心血管疾病]