中国免疫学杂志2025，Vol.41Issue(11)：2567-2572,6.DOI:10.3969/j.issn.1000-484X.2025.11.002
Tim-3促进肺泡巨噬细胞线粒体自噬和抑制NLRP3炎症小体激活对脓毒症急性肺损伤保护作用的研究
Study of protective effect of Tim-3 on sepsis-induced acute lung injury by promoting mitophagy of alveolar macrophages and inhibiting NLRP3 inflammasome activation
摘要
Abstract
Objective:To investigate protective effect and mechanism of Tim-3 on sepsis-induced acute lung injury(ALI)by pro-moting mitophagy of alveolar macrophages and inhibiting activation of NLRP3 inflammasome.Methods:LPS-stimulated mouse alveo-lar macrophage(MH-S)model and sepsis-induced ALI mouse model were constructed.Tim-3 siRNA interference technique was used to knock down Tim-3 expression in MH-S cells,and anti-Tim-3 antibody mice were injected intraperitoneally to block Tim-3 function.Western blot was used to detect protein expressions of NLRP3,ASC,cleaved-caspase-1 and mitophagy-related proteins(LC3B,P62,PINK1 and Parkin)in MH-S cells and lung tissue of mice with sepsis-induced ALI.Laser confocal fluorescence staining was used to measure ROS level and mitochondrial membrane potential of MH-S cells.Pathological examination of lung tissue was performed in mice with sepsis-induced ALI in each group,and degree of lung tissue injury was evaluated by Smith scoring system.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected from mice with ALI induced by sepsis in each group.BCA protein quantification method was used to determine protein concentration in BALF.MPO activity in lung tissue was detected by colorimetry.MDA content in lung tissue was detected by TBA method.LC3B protein expression in lung tissue was detected by immunohistochemistry.Results:In mouse alveolar macrophages,Tim-3 knockdown could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins,increase ROS release,inhibit PINK1/Parkin pathway activation and LC3B protein expression,and reduce mitochondrial membrane potential.In mice with sepsis-induced ALI,Tim-3 functional blockade could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins in lung tissue,aggravate lung pathological injury and pulmonary edema,increase MPO activity and MDA content in lung tissue,and reduce positive rate of LC3B protein.Conclusion:Tim-3 plays a protective role in sepsis-induced ALI by promoting mitophagy in alveolar macrophages and inhibiting NLRP3 inflammasome activation via PINK1/Parkin.关键词
Tim-3/肺泡巨噬细胞/线粒体自噬/NLRP3炎症小体/脓毒症急性肺损伤Key words
Tim-3/Alveolar macrophages/Mitophagy/NLRP3 inflammasome/Sepsis-induced acute lung injury分类
临床医学引用本文复制引用
朱云龙,章乐,邓喜玲,张万江,吴芳,张杰,董江涛,梁粟,柳小玲,王菊,张辉,吴江东..Tim-3促进肺泡巨噬细胞线粒体自噬和抑制NLRP3炎症小体激活对脓毒症急性肺损伤保护作用的研究[J].中国免疫学杂志,2025,41(11):2567-2572,6.基金项目
国家自然科学基金项目(82060021,82360321) （82060021,82360321）
兵团重点领域科技攻关计划项目(2023AB053) （2023AB053）
兵团指导性科技计划项目(2022ZD043). （2022ZD043）
