摘要
目的:观察黄芪多糖对气虚型心力衰竭大鼠心肌细胞线粒体结构和能量代谢的影响,并探讨其潜在的分子机制。方法:通过冠脉结扎联合力竭游泳法构建气虚型心力衰竭大鼠模型,并随机分为假手术组、模型组、黄芪多糖中剂量组(30 mg/kg)、黄芪多糖高剂量组(60 mg/kg)及曲美他嗪组。通过超声心动图评估大鼠心功能[左室射血分数(LVEF)、左室短轴缩短率(LVFS)],苏木精-伊红(HE)染色观察心肌病理形态,流式细胞术检测活性氧(ROS)水平,透射电镜分析线粒体超微结构,分光光度法测定线粒体呼吸链酶活性,荧光素酶法检测ATP含量,实时聚合酶链反应(real-time PCR)检测线粒体转录因子A(TFAM)、核呼吸因子-1(NRF-1)mRNA表达。结果:与模型组比较,黄芪多糖显著改善心力衰竭大鼠心功能(LVEF、LVFS均升高,均P<0.05),减轻心肌纤维断裂和线粒体肿胀,降低ROS水平(均P<0.01),提升呼吸链酶复合物Ⅰ~Ⅳ活性(P<0.01)和腺苷三磷酸(ATP)产量(P<0.01),并上调NRF-1与TFAM基因表达(均P<0.05)。结论:黄芪多糖可能通过修复线粒体结构、增强呼吸链酶活性、减少氧化应激及上调NRF-1/TFAM的表达,改善气虚型心力衰竭大鼠心肌能量代谢障碍。
Objective:To observe the effects of Astragalus polysaccharides on myocardial mitochondrial structure and energy metabolism in rats with Qi-deficiency type heart failure and to explore the potential molecular mechanisms.Methods:A rat model of Qi-deficiency type heart failure was established by coronary artery ligation combined with exhaustive swimming.Rats were randomly divided into a sham operation group,model group,Astragalus polysaccharides medium-dose group(30 mg/kg),Astragalus polysaccharides high-dose group(60 mg/kg),and trimetazidine group.Cardiac function was evaluated by echocardiography,including left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS).Myocardial pathological morphology was observed by hematoxylin-eosin(HE)staining.Reactive oxygen species(ROS)levels were detected by flow cytometry.Mitochondrial ultrastructure was analyzed by transmission electron microscopy.Mitochondrial respiratory chain enzyme activities were measured by spectrophotometry.Adenosine triphosphate(ATP)content was determined by a luciferase assay.The mRNA expression levels of mitochondrial transcription factor A(TFAM)and nuclear respiratory factor-1(NRF-1)were detected by real-time polymerase chain reaction(real-time PCR).Results:Compared with the model group,Astragalus polysaccharides significantly improved cardiac function in rats with heart failure,as evidenced by increased LVEF and LVFS(both P<0.05),alleviated myocardial fiber rupture and mitochondrial swelling,reduced ROS levels(both P<0.01),enhanced the activities of respiratory chain enzyme complexesⅠtoⅣ(P<0.01),increased ATP production(P<0.01),and upregulated the gene expression of NRF-1 and TFAM(both P<0.05).Conclusion:Astragalus polysaccharides may improve myocardial energy metabolism disorders in rats with Qi-deficiency type heart failure by repairing mitochondrial structure,enhancing respiratory chain enzyme activity,reducing oxidative stress,and upregulating NRF-1/TFAM expression.
作者
周维祥
吴旸
李星星
王禹萌
庄锐
范宗静
ZHOU Weixiang;WU Yang;LI Xingxing;WANG Yumeng;ZHUANG Rui;FAN Zongjing(Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China;The Affiliated Hospital of Shaanxi University of Chinese Medicine,Shaanxi 712000,China;Tsinghua Changgeng Hospital,Tsinghua University,Beijing 102218,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)
出处
《世界中医药》
北大核心
2025年第24期4423-4431,共9页
World Chinese Medicine
基金
国家自然科学基金项目(81573900、81273692)
北京中医药新奥奖励基金课题项目(2019-XAJLJJ-019)。
关键词
黄芪多糖
心力衰竭
气虚证
线粒体
能量代谢
线粒体转录因子A
核呼吸因子-1
心功能
Astragalus polysaccharides
Heart failure
Qi-deficiency syndrome
Mitochondria
Energy metabolism
Mitochondrial transcription factor A
Nuclear respiratory factor 1
Cardiac function
