【摘要】 目的 探讨RSV感染后HO1在小鼠肺部炎症中的作用。方法 构建RSV感染小鼠模型，肺组织提取RNA进行转录组测序（RNA-seq）并行差异基因分析。HE染色及BALF细胞计数观察小鼠肺组织炎症情况。通过免疫组化、Western blot及qRT-PCR检测HO1表达变化；qRT-PCR检测炎症因子水平。预测HEMIN靶蛋白并进行GO和KEGG富集分析；流式细胞术与免疫荧光检测肺泡上皮细胞ROS水平；透射电镜观察溶酶体变化以及qRT-PCR检测炎症因子水平。结果 RSV感染小鼠肺组织中HO1表达增加，诱导HO1表达减轻小鼠肺组织病理，炎症因子IL-6和TNF-α表达水平降低。RSV感染促进肺上皮细胞ROS释放与积累，使自噬溶酶体增加。诱导HO1表达可促进上皮细胞ROS清除，减少自噬溶酶体数量及细胞因子IL-6、IL-8、CXCL-10的水平。结论 HO1可抑制RSV感染后氧化应激及炎症反应。更多还原

【Abstract】 This study aims to investigate the role and specific mechanisms of HO1 in mitigating lung inflammation after RSV infection. An RSV-infected mouse model was established, and lung tissues were collected for RNA-seq and differential gene expression analysis. HE staining and BALF cell counting were used to observe inflammation in the mouse lung tissues. Changes in HO1 expression were detected through immunohistochemistry, Western blotting, and qRT-PCR;inflammatory cytokine levels were assessed using qRT-PCR. HEMIN target proteins were predicted and analyzed by underwent GO and KEGG enrichment test; ROS levels in alveolar epithelial cells were measured using flow cytometry and immunofluorescence. Lysosomal changes were observed using transmission electron microscopy. The results demonstrated that HO1 expression was upregulated in the lung tissues of RSV-infected mice. Inducing HO1 expression alleviated lung tissue pathology, and lowered inflammatory cytokines IL-6 and TNF-α levels. RSV infection promoted ROS release and accumulation in lung epithelial cells, leading to an increase in autolysosomes. The induction of HO1 expression facilitated ROS clearance and reduced the number of autolysosomes. Therefore, the protective effect of HO1 against oxidative stress reduces intracellular ROS generation, maintains organelle homeostasis, and reducing inflammatory cytokine IL-6, IL-8 and CXCL-10 levels.更多还原