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达原饮对RSV寒湿郁肺证小鼠肺部损伤和肠道菌群的影响                                                                 Δ



          张 茹 ,杜海涛 ,王晓雪 ,王 仪 ,周 倩 ,刘善新 ,王 平 (1.山东中医药大学药学院,济南 250355;
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          2.山东省中医药研究院,济南 250014)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)24-3000-06
          DOI  10.6039/j.issn.1001-0408.2023.24.08
          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。
          关键词  达原饮;呼吸道合胞病毒;寒湿郁肺证;肠道菌群


          Effects of Dayuanyin decoction on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome
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          ZHANG Ru ,DU Haitao ,WANG Xiaoxue ,WANG Yi ,ZHOU Qian ,LIU Shanxin ,WANG Ping(1. College of
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          Pharmacy,  Shandong  University  of  Traditional  Chinese  Medicine,  Jinan  250355,  China;2.  Shandong Academy
          of Chinese Medicine, Jinan 250014, China)
          ABSTRACT    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-1β in 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-1β  in  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
              Δ 基金项目 山东省重点研发计划(重大科技创新工程)项目(No.
                                                              and  Alloprevotella  were  expressed  in  high  abundance,  while
          2020CXGC010505-04);国家重点研发计划政府间国际科技创新合作
                                                              Firmicutes,  Proteobacteria,  Lachnospiraceae  NK4A136  group,
          项目(No.2019YFE0117800);山东省重点研发计划(科技示范工程)项
                                                              Kineothrix and Clostridiales unclassified were expressed in low
          目(No.2021SFGC1205)
             *第一作者 硕士研究生。研究方向:中药药理学。电话:0531-                  abundance.  After  the  intervention  of  medium-dose  DYY,  the
          82949847。E-mail:zhangru793@163.com                  relative  abundance  of  each  microbiota  tended  to  be  adjusted
              # 通信作者 研究员,硕士生导师。研究方向:中药药理学。电话:                 back,  with  different  species  including  Lachnospiraceae_UCG-
          0531-82949825。E-mail:wangpingjinan@126.com          006,  Ruminococcus,  etc.  CONCLUSIONS  Dayuanyin  decoction


          · 3000 ·    China Pharmacy  2023 Vol. 34  No. 24                            中国药房  2023年第34卷第24期
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