摘要
目的:探讨芪红胶囊基于蛋白激酶B/腺苷酸活化蛋白激酶(AKT/AMPK)-哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对缺血性心力衰竭(IHF)大鼠线粒体能量代谢的影响及调控机制。方法:将36只雄性SD大鼠随机选取6只作为假手术组,另30只作为模型组。模型组采用冠状动脉左前降支结扎法制备IHF模型。将造模成功的大鼠按体质量随机分为5组:模型组、阳性药组、芪红胶囊低剂量组[QH-L组,0.324 g/(kg·d)]、芪红胶囊中剂量组[QH-M组,0.648 g/(kg·d)]、芪红胶囊高剂量组[QH-H组,1.296 g/(kg·d)],给予相应浓度的药物溶液灌胃,假手术组、模型组给予等体积的生理盐水(10 mL/kg),各组均每日灌胃1次。连续干预4周后,选用M型超声测定左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)、短轴缩短率(FS)判定心脏结构及心功能;脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)染色法观察心肌组织病理形态;酶联免疫吸附测定法(ELISA)检测血清葡萄糖(Glu)、乳酸(LD)、酮体(KB)、游离脂肪酸(FFA)水平;线粒体膜电位检测试剂盒(JC-1法)检测细胞线粒体膜电位;线粒体通透性转换孔(mPTP)检测试剂盒检测其荧光强度;MitoSOX^(TM)Red线粒体超氧化物指示剂检测线粒体活性氧(ROS)的含量;蛋白免疫印迹法(Western Blot)检测心肌组织AKT、AMPK、mTOR的蛋白表达量。结果:与假手术组比较,模型组LVEDD、LVESD、凋亡率、Glu、LD、FFA、KB、线粒体膜电位、ROS、磷酸化AMPK(p-AMPK)蛋白表达水平均升高(P<0.05),LVEF、FS、mPTP及磷酸化AKT(p-AKT)、磷酸化mTOR(p-mTOR)蛋白表达水平均下降(P<0.05);与模型组比较,芪红胶囊低、中、高剂量组和阳性药组Glu、LD、FFA、KB、线粒体膜电位、ROS水平明显下降(P<0.05),线粒体mPTP、p-AKT蛋白表达水平明显升高(P<0.05);芪红胶囊中、高剂量组LVEDD、凋亡率、p-AMPK明显降低(P<0.05),LVEF、FS明显升高,差�
Objective:To explore the effect of Qihong capsule on mitochondrial energy metabolism in rats with ischemic heart failure(IHF)and its regulatory mechanism.Methods:Thirty-six male sprague-dawley rats were randomly divided into sham operation group(n=6)and model group(n=30).The IHF model was prepared by ligation of the left anterior descending coronary artery.Sucessfully molded rats were randomly divided into 5 groups according to their body weight:model group,positive drug group,low-dose Qihong capsule group[QH-L,0.324 g/(kg·d)],medium-dose Qihong capsule group[QH-M,0.648 g/(kg·d),high-dose Qihong capsule group[QH-H,1.296 g/(kg·d)],the rats in sham operation group and model group were given the same volume of normal saline(10 mL/kg)by gavage once a day.After four weeks of continuous intervention,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and fractional shortening of short axis(FS)were measured by M-mode ultrasound to determine the structure and function of the heart.Deoxyribonucleotide end transferase mediated notch end labeling(TUNEL)staining was used to observe the pathological morphology of myocardial tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum glucose(Glu),lactate(LD),ketone bodies(KB),and free fatty acids(FFA).Mitochondrial permeability transition pore(mPTP)detection kit was used to detect the fluorescence intensity.Mitochondrial membrane potential detection kit(JC-1 method)was used to detect mitochondrial membrane potential.MitoSOX^(TM) Red mitochondrial superoxide indicator was used to detect the content of reactive oxygen species(ROS),and Western Blot was used to detect the protein expression of protein kinase B(AKT),AMP-activated protein kinase(AMPK),and mammalian target of rapamycin(mTOR)in the myocardium.Results:Compared with sham operation group,LVEDD,LVESD,apoptosis rate,Glu,LD,FFA,KB,mitochondrial membrane potential,ROS,phosphorylated AMPK(p-AMPK)protein expression lev
作者
翟雪芹
朱鹏程
王晓峰
范辉
姜海兵
杨毅
ZHAI Xueqin;ZHU Pengcheng;WANG Xiaofeng;FAN Hui;JIANG Haibing;YANG Yi(State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,The Fourth Clinical College of Xinjiang Medical University,Urumqi,830000,China)
出处
《中西医结合心脑血管病杂志》
2024年第12期2150-2158,共9页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
新疆维吾尔自治区自然科学基金资助项目(No.2022D01C558)
省部共建中亚高发病成因与防治国家重点实验室开放课题资助项目(No.SKL-HIDCA-2021-42)。
