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基于PD-1/PD-L1信号通路探讨麦门冬汤对特发性肺纤维化小鼠的影响

Effects of Ophiopogonis Root Decoction on a mouse model of idiopathic pulmonary fibrosis based on PD-1/PD-L1 signaling pathway

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【作者】 徐梦真刘传国巩丽丽陈海红王栋朱庆均

【Author】 XU Meng-zhen;LIU Chuan-guo;GONG Li-li;CHEN Hai-hong;WANG Dong;ZHU Qing-jun;Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine;Experimental Center, Shandong University of Traditional Chinese Medicine;The Ministry of Education Key Research Center for Classical Theories of Traditional Chinese Medicine;College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine;

【通讯作者】 朱庆均;

【机构】 山东中医药大学中医药创新研究院山东中医药大学实验中心教育部中医药经典理论研究重点实验室山东中医药大学药学院

【摘要】 目的 探讨麦门冬汤对博来霉素(BLM)诱导的特发性肺纤维化(IPF)小鼠的影响,并探究其对免疫调控的作用。方法 气管滴注BLM建立IPF小鼠模型,将小鼠随机分为对照组、模型组、吡非尼酮组(0.3 g/kg)及麦门冬汤高、中、低剂量组(18、9、4.5 g/kg)。采用HE和Masson染色、ELISA法、流式细胞术和免疫组织化学法检测小鼠肺组织病理变化、Collagen I、HYP及TGF-β1水平、血浆中PD-1~+CD4~+T细胞比例、肺组织p-STAT3、PD-1、PD-L1和IL-17A表达。结果 与对照组比较,模型组小鼠肺系数升高(P<0.01),肺组织中大量炎性细胞浸润、胶原纤维沉积,肺纤维化评分升高(P<0.01),Collagen I、HYP、TGF-β1水平增加(P<0.01),血浆中PD-1~+CD4~+T细胞比例增加(P<0.01),肺组织p-STAT3、PD-1、PD-L1、IL-17A表达升高(P<0.01);与模型组比较,麦门冬汤组小鼠肺系数降低(P<0.05),肺组织炎性细胞浸润和胶原纤维沉积减少,肺纤维化评分降低(P<0.05),Collagen I、HYP、TGF-β1水平减少(P<0.05),血浆中PD-1~+CD4~+T细胞比例减少(P<0.05),肺组织p-STAT3、PD-1、PD-L1、IL-17A表达降低(P<0.05)。结论 麦门冬汤可减少细胞外基质(ECM)沉积,延缓IPF进程,其机制可能与抑制STAT3/PD-1/PD-L1免疫调控信号通路有关。

【Abstract】 AIM To investigate the effects of Ophiopogonis Root Decoction on bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF) in mice and to explore its metabolic modulation of immunity.METHODS The IPF mouse model was constructed by tracheal drip injection of BLM, and the mice were randomly divided into the control group, the model group, the pirfenidone group(0.3 g/kg) and the high, medium and low dose groups of Ophiopogonis Root Decoction(18, 9, 4.5 g/kg). HE and Masson staining, ELISA, flow cytometry and immunohistochemistry were used to detect the histopathological changes of the lung, the levels of Collagen I, HYP and TGF-β1, the proportion of PD-1+ CD4+ T cells in plasma, and the expressions of p-STAT3, PD-1, PD-L1 and IL-17A in lung tissue, respectively.RESULTS Compared with the control group, the model group displayed significantly higher level of lung coefficients(P<0.01), more severe pulmonary inflammatory cell infiltration and collagen fiber deposition, and increased pulmonary fibrosis score(P<0.01), increased levels of Collagen I, HYP and TGF-β1(P<0.01), increased proportion of PD-1+ CD4+ T cells in plasma(P<0.01), increased pulmonary expression of p-STAT3, PD-1, PD-L1 and IL-17A(P<0.01). Compared with the model group, the Ophiopogonis Root Decoction groups shared lower levels of lung coefficients(P<0.05), less pulmonary inflammatory cell infiltration and collagen fiber deposition, decreased pulmonary fibrosis score(P<0.05),decreased levels of Collagen I, HYP and TGF-β1(P<0.05), decreased proportion of PD-1+ CD4+ T cells in plasma(P<0.05), and decreased pulmonary expression of p-STAT3, PD-1, PD-L1, and IL-17A(P<0.05).CONCLUSION Ophiopogonis Root Decoction can significantly reduce extracellular matrix(ECM) deposition and curb the progression of IPF via inhibition of STAT3/PD-1/PD-L1 immunomodulatory signaling pathway.

【基金】 山东省自然科学基金(ZR2020MH384);山东省中医药科技发展计划项目(2019-0040);山东省重点研发计划(重大科技创新工程)(2020CXGC010505)
  • 【文献出处】 中成药 ,Chinese Traditional Patent Medicine , 编辑部邮箱 ,2024年02期
  • 【分类号】R285.5
  • 【下载频次】228
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