铁死亡是一种新近发现的程序性细胞死亡类型，已被证明对于脓毒症心肌病的进展起到贡献作用。虽然已经证明了miR-130b-3p作为一个抑制铁死亡并加速癌症进展的致癌基因的角色，但其在脂多糖(LPS)诱导的心肌病中对铁死亡和心肌损伤的调控作用尚未完全澄清。本研究展示了miR-130b-3p显著改善了LPS诱导的小鼠心脏功能，并改善了心脏组织的形态损伤。miR-130b-3p还改善了LPS处理的H9c2细胞的细胞存活率和线粒体功能，减少了脂质ROS和铁死亡的产生。此外，miR-130b-3p在LPS诱导的小鼠心脏组织和H9c2细胞中显著上调了GPX4表达，并抑制了ACSL4的活性。在机制上，我们使用数据库分析定位了miR-130b-3p，并通过双荧光酶报告基因实验证实了其对铁死亡相关基因ACSL4和自噬相关基因PRKAA1的抑制作用。此外，我们发现miR-130b-3p通过下调AMPK/mTOR信号通路的表达抑制了自噬的激活。同时，我们的结果表明自噬激活剂RAPA逆转了miR-130b-3p模拟物对LPS诱导的铁死亡的保护作用，而自噬抑制剂CQ发挥了协助作用，说明miR-130b-3p通过调节自噬在体外调控铁死亡的发展中起重要作用。这些发现揭示了miR-130b-3p在减轻心肌细胞铁死亡中的新功能，为改善脓毒症心肌病损伤提供了新的治疗靶点。©作者。

Ferroptosis is a newly identified type of programmed cell death that has been shown to contribute to the progression of septic cardiomyopathy. Although the role of miR-130b-3p as an oncogene that accelerates cancer progression by suppressing ferroptosis has been demonstrated, its role in the regulation of ferroptosis and cardiac injury in Lipopolysaccharide (LPS)-induced cardiomyopathy has not been fully clarified. In this study, we demonstrated that miR-130b-3p remarkably improved cardiac function and ameliorated morphological damage to heart tissue in LPS-induced mice. miR-130b-3p also improved cell viability and mitochondrial function and reduced the production of lipid ROS and ferroptosis in LPS-treated H9c2 cells. In addition, miR-130b-3p significantly upregulated GPX4 expression and suppressed ACSL4 activity in LPS-induced mouse heart tissue and H9c2 cells. Mechanistically, we used database analysis to locate miR-130b-3p and confirmed its inhibitory effects on the ferroptosis-related gene ACSL4 and autophagy-related gene PRKAA1 using a dual-luciferase reporter assay. In addition, we found that miR-130b-3p inhibited the activation of autophagy by downregulating the expression of the AMPK/mTOR signaling pathway. Meanwhile, our results show that RAPA (an autophagy activator) reverses the protective effect of miR-130b-3p mimic against LPS-induced ferroptosis, while CQ (an autophagy inhibitor) plays a facilitative role, suggesting that miR-130b-3p plays an important role in the development of ferroptosis by regulating autophagy in vitro. The findings reveal a novel function of miR-130b-3p in attenuating ferroptosis in cardiomyocytes, providing a new therapeutic target for ameliorating septic cardiomyopathy injury.© The author(s).