甘草酸对博莱霉素诱导的实验性肺纤维化的干预作用

发布时间：2019-05-22 06:26

【摘要】：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。
[Abstract]:Aim: to investigate the intervention effect of glycyrrhizic acid (GA) on bleomycin (BLM) induced pulmonary fibrosis in mice and its possible mechanism. Methods: 160 male C57BL/6J mice were randomly divided into saline (NS) group, BLM NS group and BLM GA group. The experimental pulmonary fibrosis model was established by inhaling bleomycin (2.5 mg/kg) by oral pharynx and trachea inhalation., BLM GA group and BLM NS group were given 40 mg/kg glycyrrhizic acid or saline of the same volume every day. The materials were taken on the 3rd, 7th and 14th day after operation. HE staining and Masson staining were used to observe the pathological changes and fibrosis degree of lung tissue, and flow cytometry was used to detect the proportion of circulating monocytes and alveolar macrophages. The expression of transforming growth factor 尾 1 (TGF- 尾 1) mRNA in lung tissue was detected by RT-qPCR, and the content of hydroxyproline (HYP) in lung tissue was detected by alkaline hydrolysis. Results: compared with NS group, the inflammatory infiltration and collagen content in lung tissue of BLM group and BLM NS group were significantly increased, and the experimental pulmonary fibrosis model was established successfully. Compared with the BLM NS group, the inflammatory cell infiltration and collagen fiber deposition in the lung tissue of the: BLM GA group were less, and the proportion of Ly6C~ (hi) monocyte subsets and the M2 phenotype of alveolar macrophages on the 3rd and 7th day and the 7th and 14th day were significantly decreased (P01). The expression of TGF- 尾 1 mRNA and the content of HYP in lung tissue were significantly decreased (P 0.01). Conclusion: GA can reduce the inflammatory response and collagen fiber deposition induced by bleomycin in mouse lung tissue, which may be related to the phenotypic shift and regulation of monocyte macrophage induced by GA and the down-regulation of TGF- 尾 1 expression in lung tissue.
【作者单位】：天津中医药大学研究生院;中国人民武装警察部队后勤学院附属医院呼吸与重症医学科;锦州医科大学武警后勤学院附属医院研究生培养基地;中国人民武装警察部队后勤学院附属医院心脏医院;
【基金】：国家自然科学基金资助项目(No.81102088;No.81441101;No.81570335) 天津市自然科学基金资助项目(No.15JCZDJC35000) 武警后勤学院附属医院重点项目(No.FYZ201510;No.FYZ201605)
【分类号】：R563

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