目的 探讨miR-370-3p/Sestrin2（SESN2）调控脂多糖（lipopolysaccharide，LPS）诱导的小鼠肺泡上皮细胞（alveolar epithelial cells，AECs）凋亡的机制。 方法 将C57BL/6J小鼠随机分为LPS+anti-NC组和LPS + miR-370-3p抑制剂（anti-miR-370-3p）组，每组12只。通过气管内注射LPS（5 mg/kg）来诱导急性肺损伤（acute lung injury，ALI）。分别通过小鼠尾静脉注射anti-miR-370-3p或anti-NC。MLE12细胞随机分为对照组（Con+anti-NC）、Con+anti-miR-370-3p组、LPS+anti-NC组、LPS+anti-miR-370-3p组、LPS+si-SESN2+anti-miR-370-3p组。使用定量实时PCR分析肺组织或细胞中miR-370-3p。通过测量线粒体形态学和线粒体膜电位考察miR-370-3p敲低对LPS诱导的线粒体功能障碍的保护作用。双荧光素酶报告分析证实了miR-370-3p和SESN2之间的靶向关系。 结果 与LPS+anti-NC组相比，LPS+anti-miR-370-3p组肺组织中miR-370-3p表达、丝氨酸苏氨酸激酶3（receptor-interacting serine/threonine-protein kinase 3，RIPK3）、混合系列蛋白激酶样结构域（mixed lineage kinase domain-Like，MLKL）蛋白水平、肺部炎症评分明显降低（P<0.05），和肺组织中肺表面活性蛋白C（surfactant protein C，SPC）蛋白水平明显增加（P<0.001）。与LPS+anti-NC组相比，LPS+anti-miR-370-3p组MLE12细胞中RIPK3、MLKL蛋白表达、PI阳性细胞百分比明显降低（P<0.05），并且线粒体片段化和线粒体膜电位明显增加（P<0.05）。miR-370-3p对SESN2-WT报道基因的荧光素酶活性具有抑制作用。与LPS+anti-miR-370-3p组相比，LPS+si-SESN2+anti-miR-370-3p组线粒体片段化和线粒体膜电位均明显降低（P<0.05）。 结论 miR-370-3p/SESN2轴通过介导线粒体断裂和损害线粒体功能促进LPS诱导的ALI期间AECs坏死性凋亡。

Objective To investigate the mechanism of miR-370-3p/Sestrin2（SESN2） regulating the apoptosis of mouse alveolar epithelial cells（AECs） induced by lipopolysaccharide（LPS）. Methods C57BL/6J mice were randomly divided into LPS+anti-NC group and LPS+miR-370-3p inhibitor（anti-miR-370-3p） group，with 12 mice in each group. LPS（5 mg/kg） was given by intratracheal injection to induce acute lung injury（ALI），and anti-miR-370-3p or anti-NC was injected via the caudal vein of mice. MLE12 cells were randomly divided into control group（Con+anti-NC），Con+anti-miR-370-3p group，LPS+anti-NC group，LPS+anti-miR-370-3p group，and LPS+si-SESN2+anti-miR-370-3p group. Quantitative real-time PCR was used to analyze miR-370-3p in lung tissue or cells. Mitochondrial morphology and mitochondrial membrane potential were measured to investigate the protective effect of miR-370-3p knockdown against LPS-induced mitochondrial dysfunction. Dual-luciferase reporter assay confirmed the targeting relationship between miR-370-3p and SESN2. Results Compared with the LPS+anti-NC group，the LPS+anti-miR-370-3p group had significant reductions in the expression of miR-370-3p and the protein expression levels of receptor-interacting serine/threonine-protein kinase 3（RIPK3） and mixed lineage kinase domain-like（MLKL） in lung tissue，as well as a significant reduction in lung inflammation score（P<0.05） and a significant increase in the protein expression level of surfactant protein C（SPC） in lung tissue（P<0.001）. Compared with the LPS+anti-NC group，the LPS+anti-miR-370-3p group had significant reductions in the protein expression levels of RIPK3 and MLKL in MLE12 cells and the percentage of PI-positive cells（P<0.05），as well as significant increases in mitochondrial fragmentation and mitochondrial membrane potential（P<0.05）. MiR-370-3p could inhibit the luciferase activity of SESN2-WT reporter gene. Compared with the LPS+anti-miR-370-3p group，the LPS+Si-SEN2+anti-miR-370-3p group had significant reductions in mitochondrial fragmentation and mitochondrial membrane potential（P<0.05）. Conclusion The miR-370-3p/SESN2 axis promotes the necrotizing apoptosis of AECs during ALI induced by LPS by mediating mitochondrial breakage and damaging mitochondrial function.