为了探讨转录因子PU.1在肺纤维化小鼠体内的表达情况及其对肺纤维化的影响。通过对C57BL/6小鼠建立肺纤维化模型，将小鼠随机分为对照组（生理盐水干预）10只、模型组（博来霉素干预）10只、治疗组（博来霉素+DB1976干预）10只，造模后第21天处死小鼠并取材。采用苏木精-伊红染色（hematoxylin-eosin staining, HE）、Masson染色方法观察小鼠肺组织的病理改变并进行肺泡炎和肺纤维化评分；酶联免疫吸附试验（enzyme linked immunosorbent assay, ELISA）方法检测肺泡灌洗液PU.1、血清羟脯氨酸（hydroxyproline, HYP）的表达；qPCR方法检测肺组织中PU.1的表达以及巨噬细胞标志物Fizz-1、IL-10、CD86、IL-6的表达情况。实验结果使用SPSS 26.0进行统计分析。结果表明：与对照组相比，模型组和治疗组小鼠肺组织出现明显纤维化改变，胶原沉积更为明显，纤维化评分更高；模型组小鼠肺泡灌洗液PU.1、血清HYP的表达相比对照组明显升高（P < 0.05），治疗组的PU.1、HYP相比模型组表达下降（P < 0.05），并且肺泡炎评分、纤维化评分较模型组下降（P < 0.05）；与对照组相比，模型组体内M1、M2型巨噬细胞标志物Fizz-1、IL-10、CD86、IL-6均出现增高；治疗组相比模型组肺组织内M2型巨噬细胞标记物Fizz-1、IL-10明显下降（P < 0.05），M1型巨噬细胞标记物CD86、IL-6虽然有所下降，但差异无统计学意义。可见转录因子PU.1可能通过调控M2型巨噬细胞极化参与肺纤维化的加重，PU.1抑制剂DB1976可以通过抑制肺内PU.1的表达，从而抑制M2型巨噬细胞的极化延缓肺纤维化的进程。

To investigate the expression of the transcription factor PU.1 in mice with pulmonary fibrosis, and investigate its impact on this disease. The pulmonary fibrosis model of C57BL/6 mice was established, and the mice were randomly divided into 10 control group (normal saline intervention), 10 model group (bleomycin intervention), and 10 treatment group (bleomycin + DB1976 intervention). The mice were killed on the 21st day after modeling and samples were collected. Hematoxylin-eosin staining(HE) and Masson staining were used to observe the pathological changes of mouse lung tissue and score pulmonary fibrosis and alveolitis. The expression of PU.1 in alveolar lavage fluid and hydroxyproline(HYP) in serum was detected by ELISA. The expression of PU.1 and macrophage markers Fizz-1, IL-10, CD86 and IL-6 in lung tissues were detected by qPCR. The experimental results were statistically analyzed using SPSS 26.0. The results show that compared with the control group, the lung tissue of mice in the model group and the treatment group show obvious fibrosis changes, collagen deposition is more obvious, and fibrosis score is higher. Compared with the control group, the expressions of PU.1 and HYP in the model group significantly increase(P < 0.05), while the expressions of PU.1 and HYP in the treatment group decrease(P < 0.05), and the scores of alveolar inflammation and fibrosis decrease(P < 0.05). Compared with the control group, M1 and M2 macrophage markers Fizz-1, IL-10, CD86 and IL-6 increase in the model group. Compared with model group, M2 macrophage markers Fizz-1 and IL-10 in lung tissue significantly decrease in treatment group (P <0.05). It is concluded that transcription factor PU.1 may participate in the exacerbation of lung fibrosis by regulating the polarization of M2-type macrophages, and the inhibitor of PU.1 DB1976 can inhibit the expression of PU.1 in the lung, thereby inhibiting the polarization of M2-type macrophages and delaying the process of pulmonary fibrosis.