甘草酸对博莱霉素诱导的实验性肺纤维化的干预作用

目的:探讨甘草酸(GA)对博莱霉素(BLM)诱导的小鼠肺纤维化的干预作用及其可能机制。方法:将160只雄性C57BL/6J小鼠随机分为生理盐水(NS)组、BLM组、BLM+NS组和BLM+GA组。通过口咽气管吸入法吸入博莱霉素(2.5 mg/kg)建立实验性肺纤维化模型,BLM+GA组及BLM+NS组每天给予40 mg/kg甘草酸或等体积的生理盐水灌胃,于术后第3、7、14、21天取材。采用HE染色和Masson染色观察肺组织病理学变化及纤维化程度,采用流式细胞术检测循环单核细胞和肺泡巨噬细胞的亚群比例变化,采用RT-qPCR检测肺组织中转化生长因子β1(TGF-β1)mRNA的表达水平,采用碱水解法检测肺组织中羟脯氨酸(HYP)含量。结果:与NS组相比,BLM组和BLM+NS组肺组织的炎症浸润及胶原含量明显增多,实验性肺纤维化模型制备成功。与BLM+NS组相比:BLM+GA组肺组织的炎症细胞浸润及胶原纤维沉积较少;第3、7天的Ly6C~(hi)单核细胞亚群比例和第7、14天肺泡巨噬细胞M2表型比例显著降低(P0.01);肺组织TGF-β1 mRNA表达量和HYP含量显著降低(P0.01)。结论:GA可以减轻博莱霉素诱导的小鼠肺组织的炎症反应和胶原纤维沉积,可能与GA对单核巨噬细胞的表型偏移和调控以及肺组织TGF-β1的表达下调有关。

Effect of glycyrrhizic acid on bleomycin-induced pulmonary fibrosis

AIM: To investigate the influence of glycyrrhizic acid (GA) on bleomycin (BLM)-induced pulmonary fibrosis. METHODS: C57BL/6 male mice were randomly divided into normal saline (NS) group, BLM group, BLM+NS group and BLM+GA group. The mice were administered with BLM (2.5 mg/kg) via oropharyngeal aspiration. GA (40 mg/kg) or NS was delivered daily via oral gavage after BLM administration. The mice were sacrificed on days 3, 7, 14 and 21. HE staining and Masson's trichrome staining were used to conduct histopathologic examination. The proportions of different circulatory monocytes subsets and polarization state of the bronchoalveolar lavage fluid (BALF) -derived alveolar macrophages (AM) were measured by flow cytometry. The mRNA expression of transforming growth factor-β1 (TGF-β1) was examined by RT-qPCR. RESULTS: Compared with BLM+NS group, GA significantly alleviated BLM-induced inflammation and collagen levels, and then decreased the proportions of Ly6C^hi monocytes on day 3, 7 and AM M2 on day 7, 14. GA effectively down-regulated the mRNA level of TGF-β1 and the content of HYP in the BLM-treated lung tissues. CONCLUSION: GA attenuates the BLM-induced pulmonary inflammation and fibrosis, which may be related to adjusting and controlling a dynamic view of mononuclear phagocyte changes and down-regulation of TGF-β1 in the lung tissues.