二甲双胍对肺纤维化模型小鼠炎症反应的影响

Impact of metformin on inflammatory response in mice with pulmonary fibrosis model

目的探讨二甲双胍对盐酸博来霉素诱导肺纤维化模型小鼠的抗炎作用。方法将6~8周龄,体重为23~25 g的48只雄性C57BL/6J小鼠(无特定病原体等级),按随机数表法分为对照组、模型组、吡非尼酮组、二甲双胍组、吡非尼酮联合二甲双胍组和还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)活性抑制剂(DPI)组,每组各8只。以盐酸博来霉素诱导肺纤维化小鼠为模型,观察各组小鼠肺组织病理改变,检测肿瘤坏死因子-α(TNF-α)的水平。结果肺组织HE和Masson染色显示盐酸博来霉素诱导的小鼠出现明显的肺纤维化。模型组、吡非尼酮组、二甲双胍组、吡非尼酮联合二甲双胍组和DPI组Ashcroft评分均高于对照组,差异有统计学意义(P<0.05);吡非尼酮联合二甲双胍组小鼠肺纤维化较模型组有减轻趋势(P<0.05)。二甲双胍可减轻盐酸博来霉素诱导的小鼠肺纤维化。当与吡非尼酮联用后,比单药干预进一步降低小鼠TNF-α水平。结论二甲双胍与吡非尼酮联用后抗炎效应增强,可在小鼠肺纤维化发生时期发挥效应,具有一定的延缓肺纤维化进展的作用。

Objective To investigate the anti-inflammatory effect of metformin on bleomycin hydrochloride-induced pulmonary fibrosis model mice.Methods A total of 48 male C57BL/6J mice(no specific pathogen grade),6 to 8 weeks of age and weighing 23-25 g,were divided into the control group,the model group,the pirfenidone group,the metformin group,the pirfenidone combined with metformin group and the reduced nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)activity inhibitor(DPI)group of 8 mice each according to the random number table method.Using bleomycin hydrochloride-induced pulmonary fibrosis in mice as a model,the pathological changes of lung tissue of each group of mice were observed and the levels of tumor necrosis factor-α(TNF-α)were detected.Results HE and Masson staining of lung tissue showed that bleomycin hydrochloride-induced obvious pulmonary fibrosis in mice.The Ashcroft scores of the model group,pirfenidone group,metformin group,pirfenidone combined with metformin group,and DPI group were higher than those of the control group,and the differences were statistically significant(P<0.05).There was a tendency for the lung fibrosis of the mice in the pirfenidone combined with metformin group to be attenuated compared with that of the model group(P<0.05).Metformin could alleviate bleomycin hydrochloride-induced pulmonary fibrosis in mice.When combined with pirfenidone,the level of TNF-αin mice was further reduced compared with single drug intervention.Conclusion The anti-inflammatory effect of metformin combined with pirfenidone is enhanced,which can play a role in the occurrence of pulmonary fibrosis in mice and has a certain role in delaying the progress of pulmonary fibrosis.