Previous studies showed that interleukin-9 (IL-9) is involved in cardiovascular diseases, including hypertension and cardiac fibrosis. This study aimed to investigate the role of IL-9 in lipopolysaccharide (LPS)-induced myocardial cell (MC) apoptosis. Mice were treated with LPS, and IL-9 expression was measured and the results showed that compared with WT mice, LPS-treated mice exhibited increased cardiac Mø-derived IL-9. Additionally, the effects of IL-9 deficiency (IL-9−/−) on macrophage (Mø)-related oxidative stress and MC apoptosis were evaluated, the results showed that IL-9 knockout significantly exacerbated cardiac dysfunction, inhibited Nrf2 nuclear transfer, promoted an imbalance in M1 and M2 Møs, and exacerbated oxidative stress and MC apoptosis in LPS-treated mice. Treatment with ML385, a specific nuclear factor erythroid-2 related factor 2 (Nrf2) pathway inhibitor significantly alleviated the above effects in LPS-treated IL-9−/− mice. Bone marrow-derived Møs from wild-type (WT) mice and IL-9−/− mice were treated with LPS, and the differentiation and oxidative stress levels of Møs were measured. The effect of Mø differentiation on mouse MC apoptosis was also analyzed in vitro. The results showed that LPS-induced M1 Mø/M2 Mø imbalance and Mø-related oxidative stress were alleviated by IL-9 knockout but were exacerbated by ML385 treatment. The protective effects of IL-9 deficiency on the MC apoptosis mediated by LPS-treated Møs were reversed by ML-385. Our results suggest that deletion of IL-9 decreased the nuclear translocation of Nrf2 in Møs, which further aggravated Mø-related oxidative stress and MC apoptosis. IL-9 may be a target for the prevention of LPS-induced cardiac injury.

中文翻译：

---

白细胞介素9缺乏在体内和体外通过Nrf2通路影响脂多糖诱导的巨噬细胞相关氧化应激和心肌细胞凋亡

先前的研究表明，白细胞介素 9 (IL-9) 与心血管疾病有关，包括高血压和心脏纤维化。本研究旨在探讨 IL-9 在脂多糖 (LPS) 诱导的心肌细胞 (MC) 凋亡中的作用。用 LPS 处理小鼠，并测量 IL-9 表达，结果表明，与 WT 小鼠相比，LPS 处理的小鼠表现出增加的心脏 Mø 衍生的 IL-9。此外，还评估了 IL-9 缺乏 (IL-9-/-) 对巨噬细胞 (Mø) 相关氧化应激和 MC 凋亡的影响，结果表明 IL-9 敲除显着加剧了心脏功能障碍，抑制了 Nrf2 核转移，促进了 M1 和 M2 Møs 的不平衡，并加剧了 LPS 处理的小鼠的氧化应激和 MC 细胞凋亡。用 ML385 处理，一种特定的核因子 erythroid-2 相关因子 2 (Nrf2) 通路抑制剂显着减轻了 LPS 处理的 IL-9-/- 小鼠的上述作用。用 LPS 处理来自野生型 (WT) 小鼠和 IL-9-/- 小鼠的骨髓来源的 Møs，并测量 Møs 的分化和氧化应激水平。还在体外分析了 Mø 分化对小鼠 MC 凋亡的影响。结果表明，LPS 诱导的 M1 Mø/M2 Mø 失衡和 Mø 相关的氧化应激通过 IL-9 敲除得到缓解，但通过 ML385 处理加剧。ML-385 逆转了 IL-9 缺乏对 LPS 处理的 Møs 介导的 MC 凋亡的保护作用。我们的研究结果表明，IL-9 的缺失降低了 Møs 中 Nrf2 的核转位，这进一步加剧了 Mø 相关的氧化应激和 MC 细胞凋亡。