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目的 探讨血红素加氧酶1(HMOX1)调控NF-κB/STAT3信号通路对脓毒症诱导的急性肺损伤（SIALI）的作用机制。方法 以盲肠结扎穿孔术（CLP）构建ALI动物模型，LPS刺激肺动脉内皮细胞（HPAECs）构建体外模型。采用qRT-PCR检测HMOX1表达；Western blotting检测蛋白表达；HE和和Masson染色分析肺组织病理学变化；免疫组化检测Ki 67和HMOX1的表达；ELISA检测炎性因子水平；TUNEL检测细胞凋亡。结果HMOX1在ALI患者血清、模型大鼠肺组织和LPS刺激的HPAECs中高表达。过表达HMOX1可显著改善肺组织损伤、降低炎性因子水平及细胞凋亡率，并抑制NF-κB/STAT3信号通路的磷酸化激活；而NF-κB抑制剂BAY11-7082可部分逆转HMOX1的保护效应。结论 HMOX1通过阻断NF-κB/STAT3信号通路的活化，从而有效改善ALI。本研究为将HMOX1作为治疗SIALI的潜在靶点提供了实验依据。
Abstract：Objective To investigate the mechanism of heme oxygenase-1(HMOX1) in sepsis-induced acute lung injury(SIALI) by regulating the NF-κB/STAT3 signaling pathway. Methods An animal model of ALI was established using cecal ligation and puncture(CLP), and an in vitro model was constructed by stimulating human pulmonary artery endothelial cells(HPAECs) with lipopolysaccharide(LPS). HMOX1 expression was detected by quantitative real-time PCR(q RT-PCR). Protein expression was measured by Western blotting. Pathological changes in lung tissue were analyzed by hematoxylin-eosin(HE) and Masson staining. The expression of Ki-67 and HMOX1 was detected by immunohistochemistry. Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay(ELISA). Cell apoptosis was assessed by TUNEL assay. Results HMOX1 was highly expressed in the serum of ALI patients, lung tissues of model rats, and LPS-stimulated HPAECs. Overexpression of HMOX1 significantly ameliorated lung tissue injury, reduced inflammatory cytokine levels and the apoptosis rate, and inhibited the phosphorylation-mediated activation of the NF-κB/STAT3 signaling pathway. Conversely, the NF-κB inhibitor BAY 11-7082 partially reversed the protective effects of HMOX1. Conclusion HMOX1 effectively ameliorates ALI by blocking the activation of the NF-κB/STAT3 signaling pathway. This study provides experimental evidence for targeting HMOX1 as a potential therapeutic strategy for SIALI.
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基本信息:
DOI：10.13919/j.issn.2095-6274.ZHJY202505054
中图分类号:R459.7;R563.8
引用信息:
[1]张红梅,钱克俭.HMOX1阻断NF-κB/STAT3信号通路缓解脓毒症引起急性肺损伤的机制研究[J].中华灾害救援医学,2025,12(07):771-774.DOI:10.13919/j.issn.2095-6274.ZHJY202505054.