首页|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

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

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

Ophiopogonis Root Decoctionidiopathic pulmonary fibrosisbleomycinimmunomodulationSTAT3/PD-1/PD-L1 signaling pathway

徐梦真、刘传国、巩丽丽、陈海红、王栋、朱庆均

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山东中医药大学中医药创新研究院, 山东 济南 250355

山东中医药大学实验中心, 山东 济南 250355

教育部中医药经典理论研究重点实验室, 山东 济南 250355

山东中医药大学药学院,山东 济南 250355

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麦门冬汤 特发性肺纤维化 博来霉素 免疫调控 STAT3/PD-1/PD-L1 信号通路

山东省自然科学基金山东省中医药科技发展计划项目山东省重点研发计划(重大科技创新工程)

ZR2020MH3842019-00402020CXGC010505

2024

中成药
国家食品药品监督管理局,信息中心中成药信息站,上海中药行业协会

中成药

CSTPCD北大核心
影响因子:1.217
ISSN:1001-1528
年,卷(期):2024.46(2)
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