Asprosin Protects H9c2 Cells from Hypoxia/Reoxygenation Induced Injury by Promoting Mitophagy

目的：急性心肌梗死是全球死亡的主要原因之一。经皮冠状动脉介入治疗是恢复受影响心肌血流的主要治疗方法，但再灌注可能导致心肌损伤，影响急性心肌梗死患者预后。白脂素是一种新发现的脂肪因子，其在心肌保护方面的作用尚需进一步研究。方法：对H9c2细胞进行缺氧/复氧(H/R)处理，并用不同浓度的白脂素预处理。通过测量细胞内活性氧(ROS)、CCK-8和乳酸脱氢酶(LDH)水平评估细胞损伤程度。之后通过测定线粒体自噬的相关蛋白的表达及线粒体膜电位的改变，并加入线粒体自噬抑制剂组进行对比，明确白脂素对心肌的保护作用及对心肌线粒体自噬的影响。结果：白脂素降低了ROS水平，提高了细胞活性，升高了H/R后细胞内PINK1蛋白的表达，稳定了细胞内线粒体的功能及活性。在加入线粒体自噬抑制剂后，抑制了白脂素对H/R后细胞的保护作用，PINK1蛋白表达下降，线粒体功能及活性明显下降。结论：本研究证实了白脂素在H/R损伤心肌细胞后的保护作用，并可能是通过在心肌细胞H/R期间促进线粒体自噬以起到保护作用。Objective: Acute myocardial infarction (AMI) is a leading cause of death globally. Percutaneous coronary intervention is the primary treatment to restore blood flow to affected myocardium, but reperfusion may cause myocardial injury, impacting the prognosis of AMI patients. Asprosin, a newly identified adipokine, requires further study for its cardioprotective effects. Methods: H9c2 cells were exposed to hypoxia/reoxygenation (H/R) and pretreated with varying asprosin concentrations. Cell damage was assessed by measuring intracellular reactive oxygen species (ROS), CCK-8 results, and lactate dehydrogenase (LDH) levels. Mitophagy-related protein expression and mitochondrial membrane potential changes were examined, and a mitophagy inhibitor was used for comparison to clarify asprosin’s cardioprotective role and its impact on myocardial mitophagy. Results: Asprosin reduced ROS levels, enhanced cell viability, upregulated PINK1 protein expression after H/R, and stabilized mitochondrial function and activity. The mitophagy inhibitor attenuated asprosin’s protective effects, decreasing PINK1 expression and significantly impairing mitochondrial function and activity. Conclusion: This study confirms asprosin’s protective effects on H/R-damaged myocardial cells, likely through promoting mitophagy during H/R in cardiomyocytes.