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目的:探讨细胞外信号调节蛋白激酶5(ERK5)是否在体内外参与肺纤维化的发病过程，进一步探讨ERK5对体外培养的人肺成纤维细胞自噬的调控。方法:BIX02189(ERK5抑制剂)处理人肺成纤维细胞，用转化生长因子βn 1(TGF-βn 1)诱导其表型转化。实验细胞分为6组：DMSO组、BIX02189组、DMSO＋TGF-βn 1组、BIX02189＋TGF-βn 1组、BIX02189＋TGF-βn 1＋3-MA组和3-MA对照组。蛋白质印迹检测表型转化标志因子Fibronectin、α-平滑肌肌动蛋白(α-SMA)和自噬相关蛋白LC3Ⅱ、Beclin-1、p62的表达。将24只雄性C57B/L小鼠随机分为生理盐水对照组(NS组)、博来霉素模型组(BLM组)、BIX02189治疗组(BT组)和BIX02189对照组(BC组)。于造模当日起每日观察小鼠一般状态，于28 d后处死小鼠，取左侧肺组织行Masson染色和HE染色，取右侧肺组织通过蛋白质印迹检测ERK5、α-SMA、LC3Ⅱ的表达。n 结果:BIX02189＋TGF-βn 1组与DMSO＋TGF-βn 1组相比，α-SMA、p62蛋白表达水平降低，LC3Ⅱ、Beclin-1蛋白表达水平升高；应用自噬抑制剂后，α-SMA蛋白表达水平升高。NS组和BC组小鼠一般状态良好，BLM组一般状态差，BT组小鼠一般状态稍好。Masson染色和HE染色显示，BT组较BLM组肺泡间隔变窄，蓝色的胶原纤维沉积量减少，纤维化程度减轻。蛋白质印迹结果显示，BT组α-SMA的蛋白表达量明显低于BLM组；BT组LC3Ⅱ蛋白表达量高于BLM组。n 结论:ERK5抑制剂促进人肺成纤维细胞自噬并抑制其表型转化，改善博来霉素诱导的小鼠肺纤维化。“,”Objective:To investigate whether extracellular signal-regulated protein kinase-5 (ERK5) is involved in the pathogenesis of pulmonary fibrosis in vitro and in vivo, and to further explore the regulation of ERK5 on autophagy of human lung fibroblasts in vitro.Methods:Human lung fibroblasts was treated with BIX02189 (ERK5 inhibitor), transforming growth factor-βn 1 (TGF-βn 1) was used to induce phenotypic transformation.The experimental cells were divided into six groups: dimethyl sulfoxide (DMSO) group, BIX02189 group, DMSO+ TGF-βn 1 group, BIX02189+ TGF-βn 1 group, BIX02189+ TGF-βn 1+ 3-MA group and 3-MA control group.The expressions of phenotypic markers fibronectin, α-smooth muscle actin (α-SMA) and autophagy-related proteins (LC3Ⅱ), Beclin-1, p62 were detected by Western blot.Twenty-four male C57B/L mice were randomly divided into normal saline control group (NS group), bleomycin model group (BLM group), BIX02189 treatment group (BT group), and BIX02189 control group (BC group). The general state of the mice was observed daily from the day of modeling.The mice were sacrificed after 28 days.The left lung tissue was taken for Masson staining and HE staining.The right lung tissue was taken for Western blot to detect the expressions of ERK5, α-SMA, and LC3Ⅱ.n Results:Compared with DMSO+ TGF-βn 1 group, the expressions of α-SMA and p62 were decreased, and the expressions of LC3Ⅱ and Beclin-1 were increased in BIX02189+ TGF-β n 1 group.After the application of autophagy inhibitors, the expression of α-SMA was increased.The general state of the mice in the NS group and BC group was good, the general state of the BLM group was poor, and the general state of the BT group was a little better.Masson staining and HE staining showed that compared with the BLM group, the alveolar septum was narrower, the amount of blue collagen fibers was decreased, and fibrosis was reduced in the BT group.Western blot results showed that the expression of α-SMA in the BT group was significantly lower than that in the BLM group, the expression of LC3Ⅱ in the BT group was higher than that in the BLM group.n Conclusions:ERK5 inhibitors may inhibit the phenotypic transformation of fibroblasts by promoting cell autophagy, thereby alleviate pulmonary fibrosis.