Inflammation plays a crucial role in sepsis‐induced cardiac injury. The purpose of this study was to determine whether interleukin‐5 (IL‐5) affected lipopolysaccharide (LPS)‐induced cardiac injury by regulating the inflammatory response. First, the expression level and source of cardiac IL‐5 were examined, and the results showed that LPS treatment and cecal ligation decreased cardiac IL‐5 expression in macrophages. In addition, LPS was used to establish a mouse sepsis model, and the effects of IL‐5 deletion on cardiac injury, M1 macrophage differentiation and myocardial cell apoptosis were analyzed. The results showed that IL‐5 deficiency significantly increased cardiac injury marker expression, worsened cardiac dysfunction, promoted M1 macrophage differentiation and exacerbated myocardial cell apoptosis in LPS‐induced septic mice. The nuclear factor‐kappa B (NF‐κB) p65 pathway was inhibited by JSH‐23, and the results showed that treatment with JSH‐23 inhibited M1 macrophage differentiation and alleviated cardiac injury in LPS‐treated IL‐5‐knockout mice. Furthermore, the effects of IL‐5 deficiency on M1 macrophage differentiation and myocardial cell apoptosis were measured in vitro. The IL‐5‐mediated promotion of M1 macrophage differentiation was also reversed by S31‐201, and the pro‐apoptotic effect of IL‐5 knockout on macrophage‐mediated myocardial cell apoptosis was also reversed by JSH‐23. In conclusion, we found that IL‐5 knockout may exacerbate sepsis‐induced cardiac injury by promoting M1 macrophage differentiation in mice. IL‐5 may be a potential target for the clinical prevention of sepsis‐related cardiac injury.

中文翻译：

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Interleukin-5 缺失促进败血症诱导的 M1 巨噬细胞分化，恶化心脏功能障碍，并通过 NF-κB p65 途径加剧小鼠的心脏损伤

炎症在脓毒症引起的心脏损伤中起着至关重要的作用。本研究的目的是确定白细胞介素 5 (IL-5) 是否通过调节炎症反应影响脂多糖 (LPS) 诱导的心脏损伤。首先，检查了心脏IL-5的表达水平和来源，结果表明LPS治疗和盲肠结扎降低了巨噬细胞中心脏IL-5的表达。此外，利用LPS建立小鼠脓毒症模型，分析IL-5缺失对心脏损伤、M1巨噬细胞分化及心肌细胞凋亡的影响。结果表明，IL-5缺乏显着增加了LPS诱导的脓毒症小鼠心脏损伤标志物的表达，加重了心脏功能障碍，促进了M1巨噬细胞分化，加剧了心肌细胞凋亡。JSH-23抑制核因子-κB（NF-κB）p65通路，结果表明JSH-23治疗抑制了LPS治疗的IL-5基因敲除小鼠的M1巨噬细胞分化并减轻了心脏损伤。此外，在体外测量了IL-5缺乏对M1巨噬细胞分化和心肌细胞凋亡的影响。S31-201 也逆转了 IL-5 介导的 M1 巨噬细胞分化的促进作用，JSH-23 也逆转了 IL-5 敲除对巨噬细胞介导的心肌细胞凋亡的促凋亡作用。总之，我们发现 IL-5 敲除可能通过促进小鼠 M1 巨噬细胞分化加剧败血症诱导的心脏损伤。IL-5 可能是临床预防脓毒症相关心脏损伤的潜在靶点。