河北医学2025，Vol.31Issue(5)：717-723,7.DOI:10.3969/j.issn.1006-6233.2025.05.03
美托洛尔调控PGC1α-PPARα-mTOR信号通路介导心肌能量代谢改善大鼠慢性心力衰竭
Metoprolol-Mediated Improvement of Myocardial Energy Metabolism via PGC1α-PPARα-mTOR Signaling Pathway in Rats with CHF
摘要
Abstract
Objective:To investigate the effect of metoprolol on myocardial energy metabolism in rats with chronic heart failure(CHF)by regulating the peroxisome proliferator-activated receptor coactivator 1α(PGC1α)-peroxisome proliferator-activated receptor α(PPARα)-mammalian target of rapamycin(mTOR)signaling pathway.Methods:CHF rat models were established by coronary artery ligation.Rats were randomly divided into sham operation group(only sutured without ligation),model group,captopril group(2.57 mg/kg captopril gavage),low-dose metoprolol group(10 mg/kg),and high-dose metoprolol group(20 mg/kg),with 15 rats in each group.After 4 weeks of continuous treatment,cardiac function was evaluated by echocardiography;serum myocardial injury-related indicators were detected using ELISA kits;myocardial his-topathological changes were observed by hematoxylin-eosin(HE)and Masson trichrome staining;myocardial cell apoptosis was observed by TUNEL staining;myocardial energy metabolism-related indicators were detec-ted by colorimetry;and the expression of proteins related to the PGC1α-PPARα-mTOR signaling pathway was analyzed by Western blot.Results:Compared with the sham operation group,the model group showed massive inflammatory infiltration and blue collagen fiber deposition in myocardial cells,significantly decreased levels of LVEF,LVFS,glycogen mass fraction,ATP concentration,PGC1α,PPARα,and p-mTOR(P<0.05),and significantly increased LVESD,LVEDD,CK-MB,cTnT,myocardial cell apoptosis ratio,fatty acid(FA),and lactate levels(P<0.05).Compared with the model group,the low-dose and high-dose metopro-lol groups and the captopril group exhibited varying degrees of alleviated myocardial cell injury,reduced colla-gen deposition in myocardial cells,significantly increased LVEF,LVFS,glycogen mass fraction,ATP con-centration,PGC1α,PPARα,and p-mTOR levels(P<0.05),and significantly decreased LVESD,LVEDD,CK-MB,cTnT,myocardial cell apoptosis ratio,FA,and lactate levels(P<0.05).Compared with the low-dose metoprolol group and the captopril group,the high-dose metoprolol group had less collagen deposition in myocardial cells,significantly higher LVEF,LVFS,glycogen mass fraction,ATP concentration,PGC1α,PPARα,and p-mTOR levels(P<0.05),and significantly lower LVESD,LVEDD,CK-MB,cTnT,myocar-dial cell apoptosis ratio,FA,and lactate levels(P<0.05).Conclusion:Metoprolol mediates myocardial cell energy metabolism by activating the PGC1α-PPARα-mTOR signaling pathway,alleviates pathological dam-age of myocardial cells in CHF rats,and thus improves cardiac function in CHF rats.关键词
慢性心力衰竭/美托洛尔/PGC1α-PPARα-mTOR信号通路/心肌能量代谢Key words
Chronic heart failure/Metoprolol/PGC1α-PPARα-mTOR signaling pathway/Myocardial energy metabolism引用本文复制引用
于新龙,贾丽丽,姚月娟,高凡茸..美托洛尔调控PGC1α-PPARα-mTOR信号通路介导心肌能量代谢改善大鼠慢性心力衰竭[J].河北医学,2025,31(5):717-723,7.基金项目
河北省重点研发计划项目,(编号:21018310510D) （编号:21018310510D）
