西南医科大学学报2025，Vol.48Issue(5)：471-477,7.DOI:10.3969/j.issn.2096-3351.2025.05.006
OPA1在香烟烟雾诱导的小鼠气道炎症和氧化应激中的作用及其机制研究
The Role and Mechanism of OPA1 in Cigarette Smoke-Induced Airway Inflammation and Oxidative Stress in Mice
摘要
Abstract
Objective The study aimed to investigate the effects and mechanisms of optic atrophy protein-1(OPA1)on ciga-rette smoke(CS)-induced airway inflammation and oxidative stress in mice.Methods C57BL/6 mice were randomly divided into four groups:control group,OPA1 overexpression(OPA1 OE)group,CS-exposed group,and OPA1 OE+CS-exposed group.The control group and the CS-exposed group received intranasal AAV-GFP via aerosol inhalation,followed by exposure to air and CS,respec-tively.The OPA1 OE group and the OPA1 OE+CS-exposed group received intranasal AAV-OPA1 via aerosol inhalation,followed by exposure to air and CS,respectively.After four weeks,bronchoalveolar lavage fluid(BALF)of all mice were collected for total cells,neutrophils,and macrophages counts.Inflammatory cytokines(TNF-α,IL-6 and IL-1β)in BALF were measured using enzyme-linked immunosorbent assays(ELISA).The lung tissues of all mice were collected for histopathological examination,and the expres-sion of mitochondrial dynamics-related proteins(OPA1,MFN2,DRP1 and MFF)were detected by western blot.The malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in lung tissues of all mice were also measured.Then mRNA sequencing and bio-informatics analysis were performed on the lung tissues of the CS-exposed group and OPA1 OE+CS-exposed group.Results Compared the CS group with the control group,airway inflammatory changes and mucus secretion significantly increased,the number of total cells,neutrophils and macrophages as well as the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)in the BALF significantly increased;MDA increased and SOD decreased;the expression of mitochondrial fission proteins(DRP1 and MFF)upregulated,and the expression of mitochondrial fusion proteins(MFN2 and OPA1)downregulated.The difference was statistically significant(P<0.05).Compared the OPA1 OE+CS group with the CS group,airway inflammatory changes and mucus secretion significantly decreased,the number of total cells,neutrophils and macrophages as well as the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)in the BALF significantly decreased;MDA decreased and SOD increased;the expression of DRP1 and MFF downregulated,and the expression of OPA1 upregulated.The difference was statistically significant(P<0.05).While,there was no statistically signifi-cant difference in MFN2 protein expression level(P>0.05).Compared the OPA1 group with the control group,the expression of OPA1 significantly upregulated(P<0.05).However,appeal inflammatory changes,mucus secretion,oxidative stress and other mito-chondrial protein expression levels were not significant(P>0.05).mRNA sequencing of lung tissues from the CS-exposed group and OPA1 OE+CS-exposed group revealed 136 upregulated genes and 91 downregulated genes(P<0.05).The KEGG pathway enrichment analysis demonstrated that OPA1 exerts anti-inflammatory effects under conditions of CS exposure,involving multiple signaling path-ways,including TNF,cAMP,AMPK,and PPAR signaling.Conclusion OPA1 significantly ameliorated CS-induced airway inflam-mation and oxidative stress in mice,and the underlying mechanism may be associated with improved mitochondrial function.关键词
视神经萎缩蛋白-1/香烟/线粒体/气道炎症/氧化应激Key words
OPA1/Cigarette/Mitochondria/Airway inflammation/Oxidative stress分类
医药卫生引用本文复制引用
曾婷婷,胡雪茹,刘志雄,秦江月,高丽娟,陈珍妮,刘潋,申永春,文富强..OPA1在香烟烟雾诱导的小鼠气道炎症和氧化应激中的作用及其机制研究[J].西南医科大学学报,2025,48(5):471-477,7.基金项目
国家自然科学基金(82170046,82300050) （82170046,82300050）
华西医院1·3·5工程项目(RHM24207) （RHM24207）
四川省科技厅项目(2024NSFSC1522,2025ZNSFSC1543) （2024NSFSC1522,2025ZNSFSC1543）
