Isoliquiritigenin attenuates myocardial ischemia reperfusion through autophagy activation mediated by AMPK/mTOR/ULK1 signaling.

Autor: Shen L; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China., Zhu Y; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China., Chen Z; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China., Shen F; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China., Yu W; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China., Zhang L; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China. zhanglinbu2010@163.com.
Jazyk: angličtina
Zdroj: BMC cardiovascular disorders [BMC Cardiovasc Disord] 2024 Aug 09; Vol. 24 (1), pp. 415. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1186/s12872-024-04054-z
Abstrakt: Background: Ischemia reperfusion (IR) causes impaired myocardial function, and autophagy activation ameliorates myocardial IR injury. Isoliquiritigenin (ISO) has been found to protect myocardial tissues via AMPK, with exerting anti-tumor property through autophagy activation. This study aims to investigate ISO capacity to attenuate myocardial IR through autophagy activation mediated by AMPK/mTOR/ULK1 signaling.
Methods: ISO effects were explored by SD rats and H9c2 cells. IR rats and IR-induced H9c2 cell models were established by ligating left anterior descending (LAD) coronary artery and hypoxia/re-oxygenation, respectively, followed by low, medium and high dosages of ISO intervention (Rats: 10, 20, and 40 mg/kg; H9c2 cells: 1, 10, and 100 μmol/L). Myocardial tissue injury in rats was assessed by myocardial function-related index, HE staining, Masson trichrome staining, TTC staining, and ELISA. Autophagy of H9c2 cells was detected by transmission electron microscopy (TEM) and immunofluorescence. Autophagy-related and AMPK/mTOR/ULK1 pathway-related protein expressions were detected with western blot.
Results: ISO treatment caused myocardial function improvement, and inhibition of myocardial inflammatory infiltration, fibrosis, infarct area, oxidative stress, CK-MB, cTnI, and cTnT expression in IR rats. In IR-modeled H9c2 cells, ISO treatment lowered apoptosis rate and activated autophagy and LC3 fluorescence expression. In vivo and in vitro, ISO intervention exhibited enhanced Beclin1, LC3II/LC3I, and p-AMPK/AMPK levels, whereas inhibited P62, p-mTOR/mTOR and p-ULK1(S757)/ULK1 protein expression, activating autophagy and protecting myocardial tissues from IR injury.
Conclusion: ISO treatment may induce autophagy by regulating AMPK/mTOR/ULK1 signaling, thereby improving myocardial IR injury, as a potential candidate for treatment of myocardial IR injury.
(© 2024. The Author(s).)
Databáze: MEDLINE
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