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 histopathological 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 detected 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 metoprolol groups and the captopril group exhibited varying degrees of alleviated myocardial cell injury, reduced collagen deposition in myocardial cells, significantly increased LVEF, LVFS, glycogen mass fraction, ATP concentration, 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, myocardial 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 damage of myocardial cells in CHF rats, and thus improves cardiac function in CHF rats.
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2025, Vol. 31 
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