达原饮对RSV寒湿郁肺证小鼠肺部损伤和肠道菌群的影响  

Effects of Dayuanyin decoction on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome

作　　者：张茹 杜海涛 王晓雪 王仪 周倩[2] 刘善新[2] 王平[2] ZHANG Ru;DU Haitao;WANG Xiaoxue;WANG Yi;ZHOU Qian;LIU Shanxin;WANG Ping(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Shandong Academy of Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学药学院,济南250355 [2]山东省中医药研究院,济南250014

出　　处：《中国药房》2023年第24期3000-3005,共6页China Pharmacy

基　　金：山东省重点研发计划(重大科技创新工程)项目(No.2020CXGC010505-04);国家重点研发计划政府间国际科技创新合作项目(No.2019YFE0117800);山东省重点研发计划(科技示范工程)项目(No.2021SFGC1205)。

摘　　要：目的探讨达原饮对RSV寒湿郁肺证小鼠肺部损伤和肠道菌群的影响。方法将36只BALB/c小鼠分为正常组(NC组)、模型组(MC组)、阳性对照组(LBM组,利巴韦林57.59 mg/kg)和达原饮低、中、高剂量组(LDYY、MDYY、HDYY组,达原饮按生药量计1.67、3.34、6.68 g/kg),每组6只。除NC组外,其余各组小鼠采用“寒湿造模+RSV感染”的方式建立RSV寒湿郁肺证小鼠模型;于第2次寒湿刺激结束后,鼻腔滴注50倍半数细胞培养物感染量的RSV液,每天1次,连续3 d;各药物组于每次滴鼻4 h后灌胃相应药液,每天1次,连续5 d。检测小鼠血清中胃动素(MTL)、胃泌素(GAS)水平,肺组织上清液中白细胞介素6(IL-6)、IL-1β水平,外周血淋巴细胞百分比;观察肺组织病理形态变化并分析肠道菌群变化。结果与MC组比较,达原饮各组小鼠血清中MTL水平(HDYY组除外)和肺组织上清液中IL-6、IL-1β水平均显著降低,血清中GAS水平(HDYY组除外)均显著升高(P<0.05或P<0.01),肺组织病理状态均改善;LDYY组外周血中T淋巴细胞的百分比和MDYY组外周血中T、B淋巴细胞的百分比均显著升高(P<0.05或P<0.01)。与NC组比较,MC组中拟杆菌门、放线菌门、拟杆菌属、另枝菌属、拟杆菌纲、产酸拟杆菌、拟普雷沃氏菌属等呈高丰度表达,厚壁菌门、变形菌门、毛螺菌属NK4A136组、丝状菌属、未分类的Clostridiales等呈低丰度表达;经中剂量达原饮干预后,各菌群相对丰度均有回调趋势,其差异物种包括Lachnospiraceae_UCG-006、瘤胃球菌属Ruminococcus等。结论达原饮能够减轻RSV寒湿郁肺证小鼠的肺部损伤,其机制可能与减轻炎症、调节胃肠激素水平和淋巴细胞百分比以及肠道有益菌和有害菌的相对丰度有关。OBJECTIVE To study the effects of Dayuanyin decoction(DYY)on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome.METHODS Thirty-six BALB/c mice were divided into the normal group(NC group),model group(MC group),positive control group(LBM group,57.59 mg/kg ribavirin),DYY low-dose,medium-dose and high-dose groups(LDYY,MDYY,HDYY groups,1.67,3.34,6.68 g/kg,calculated by crude drug),with 6 mice in each group.Except for NC group,RSV-Hanshi yufei syndrome model was induced by“Hanshi modeling+RSV infection”;after the second cold and wet stimulation,RSV solution was dripped into the nasal cavity at 50%tissue culture infectious dose,once a day,for 3 consecutive days;each administration group was given corresponding solution intragastrically 4 hours after each nasal drip,once a day,for 5 consecutive days.The levels of motilin(MTL)and gastrin(GAS)in serum,the levels of IL-6 and IL-1βin supernatant of lung tissue,and the percentage of peripheral blood lymphocytes were all determined.The pathological changes of lungs were observed,and the changes of gut microbiota were analyzed.RESULTS Compared with MC group,the levels of MTL in serum(except for HDYY group),and the levels of IL-6 and IL-1βin supernatant of lung tissue were all decreased significantly in DYY groups,while the level of GAS(except for HDYY group)in serum was increased significantly(P<0.05 or P<0.01).The pathology of lung tissue was improved,the percentage of T lymphocytes in LDYY group and the percentages of T lymphocyte and B lymphocyte in MDYY group were all increased significantly(P<0.05 or P<0.01).Compared with the NC group,Bacteroidetes,Actinobacteria,Bacteroides,Alistipes,Bacteroidota,Bacteroides acidfaciens and Alloprevotella were expressed in high abundance,while Firmicutes,Proteobacteria,Lachnospiraceae NK4A136 group,Kineothrix and Clostridiales unclassified were expressed in low abundance.After the intervention of medium-dose DYY,the relative abundance of each microbiota tended to be adjusted back,with different species including

关 键 词：达原饮 呼吸道合胞病毒 寒湿郁肺证 肠道菌群 

分 类 号：R965[医药卫生—药理学]