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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (8): 1058-1066.doi: 10.12092/j.issn.1009-2501.2025.08.005

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Semaglutide alleviates hypoxia/reoxygenation-induced inflammatory injury of AC16 human cardiomyocytes by regulating autophagy through AMPK/mTOR/ULK1 pathway

JIN Lili, QIE Tao, LI Liqin   

  1. 1Baoding No.1 Central Hospital, Department of Cardiovascular 5th, Baoding 071000, Hebei, China;
    2Baoding No.1 Central Hospital, Department of Emergency 3th, Baoding 071000, Hebei, China;
    3Baoding No.1 Central Hospital, Department of Endocrinology 3th, Baoding 071000, Hebei, China
  • Received:2024-10-28 Revised:2024-12-30 Published:2025-08-12

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Abstract: AIM: To investigate the effects of semaglutide on inflammation and autophagy in human AC16 cardiomyocytes under hypoxia/reoxygenation conditions. METHODS: AC16 cells were randomly divided into four groups: control (CON), hypoxia/reoxygenation (H/R), hypoxia/reoxygenation+semaglutide (H/R+SEM), and hypoxia/reoxygenation+semaglutide+3-MA (H/R+SEM+3-MA). All groups except CON underwent 8 hours of hypoxia followed by 12 hours of reoxygenation. Cell viability was measured by CCK-8. Levels of IL-1β and TNF-α were assessed by ELISA. Western blot analysis evaluated AMPK, p-AMPK, mTOR, p-mTOR, ULK1, p-ULK1, Beclin-1, and LC3. Autophagosomes were analyzed using laser confocal microscopy and transmission electron microscopy. The structure of autophagosome and autolysosome was observed by transmission electron microscopy. RESULTS: IL-1β and TNF-α levels increased significantly in the H/R group compared to CON (P<0.01) but decreased in the H/R+SEM group (P<0.01). In the H/R+SEM+3-MA group, inflammatory levels increased compared to the H/R+SEM (P<0.05). Compared with the CON group, p-AMPK/AMPK and p-ULK1/ULK1 ratios increased significantly in the H/R group (P<0.05, P<0.01). The ratios further increased in the H/R+SEM group compared to H/R (P<0.05, P<0.01). But the two ratios decreased in the H/R+SEM+3-MA group compared to H/R+SEM (P<0.01, P<0.05). The pmTOR/mTOR had the opposite trend to the two previous ratios. The expression of Beclin1 and LC3 were significantly increased in group H/R compared to CON (P<0.05), and which further increased in the H/R+SEM group compared to H/R (P<0.01). But the two indicators decreased in the H/R+SEM+3-MA group compared to H/R+SEM (P<0.01, P<0.05). Laser confocal microscopy revealed increased autophagosome numbers in H/R group compared to CON (P<0.05), and which further increased in the H/R+SEM group compared to H/R (P<0.01). While the H/R+SEM+3-MA group showed a decrease compared to H/R + SEM (P<0.05). CONCLUSION: Semaglutide may moderate regulate autophagy through AMPK/mTOR/ULK1 pathway, reduce the release of inflammatory factors, and alleviate hypoxia/reoxygenation-induced inflammatory injury.

Key words: semaglutide, hypoxia/reoxygenation, cardiomyocytes, inflammation, autophagy

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