FOXM1 在SAP/ALI 小鼠肺组织修复过程中的变化及其意义

目的 探讨重症急性胰腺炎（SAP）急性肺损伤（ALI）修复过程中叉头框蛋白M1（FOXM1）的表达变化及其意义。方法 将BALB/c 小鼠随机分为假手术组（10 只）和模型组（50 只），模型组小鼠又随机分为模型组1、3、7、10 和14 d 5 个亚组，每组10 只。采用雨蛙肽腹腔注射诱导SAP/ALI 模型，观察肺组织病理变化、肺微血管通透性、肺组织含水量及血清淀粉酶浓度。采用实时荧光定量聚合酶链反应和Western blot 检测肺损伤修复过程中不同时间点FOXM1 mRNA 和蛋白的表达水平，分析FOXM1 蛋白表达与肺微血管通透性的相关性。结果 与假手术组比较，模型复制后各时间点肺组织形态发生改变，但随着时间的推移而不断减轻（P <0.05）。血清淀粉酶、肺微血管通透性及肺组织含水量变化规律与肺组织损伤后病理学评分改变相似。同时，肺组织FOXM1 mRNA 表达水平有明显的动态演变规律，复制后第1 天表达下调，第3 天开始逐渐上调，第7 天达高峰，第10 天逐渐恢复，第14 天时基本回到基础水平，且FOXM1 蛋白也有相似的表达规律。FoxM1 蛋白表达水平与肺微血管通透性呈负相关（P <0.05）。结论 FOXM1 可能在促进肺气血屏障的修复过程中发挥重要作用。

Change of FOXM1 in process of repair of acute lung injury ofmice with severe acute pancreatitis and its significance

Objective To investigate the expression and significance of Forkhead Box M1 (FOXM1) in theprocess of repair of acute lung injury (ALI) in mice with severe acute pancreatitis (SAP). Methods BALB/c micewere randomly divided into a sham group (10 mice) and a model group (50 mice), and the model group was thenrandomly divided into 5 subgroups, namely 1-day, 3-day, 7-day, 10-day and 14-day subgroups (10 in each). The SAP/ALI model was induced by the method of intraperitoneal injection of caerulein. The pathological changes of the lungtissues and the pulmonary microvascular permeability were observed. The water content of the lung tissues and theserum amylase level were detected. In addition, qRT-PCR and Western blot were used to detect the FOXM1 mRNAand protein expression levels respectively at different time points during the repair process of lung injury in the SAP/ALI mice. Finally, the correlation between FOXM1 protein expression and pulmonary microvascular permeabilitywas analyzed. Results Compared with the sham group, the morphology of the lung tissues changed in the modelgroup at each time point (on days 1, 3, 7, 10 and 14), the pathological changes were alleviated over time (P < 0.05). The changes of serum amylase level, pulmonary vascular permeability and water content of the pulmonary tissues were similar with the change of pathological scores after lung injury. At the same time, the expression of FOXM1 mRNA in the lung tissues had an obvious dynamic evolutional rule. The expression of FOXM1 mRNA decreased on the 1st day after modeling, then increased gradually from the 3rd day, and reached the peak on the 7th day, gradually restored on the 10th day, and returned to the baseline on the 14th day. Moreover, FOXM1 protein expression level also presented the similar rule. There was a negative correlation between the expression of FOXM1 protein and the pulmonary microvascular permeability (P < 0.05). Conclusions FOXM1 may play an important role in the repair of pulmonary blood-gas barrier.