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异钩藤碱对哮喘小鼠气道炎症的影响
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          蔡 金 ,华诏召 ,张昌容 ,黄 丹 ,张淇华 ,王 毅 ,周素芳 ,刘 莲 ,龚 安 (1.贵州中医药大学第一
          附属医院中医经典科,贵阳 550001;2.贵州中医药大学第二附属医院产科,贵阳 550002;3.贵州中医药大学
          微生态研究中心,贵阳 550001;4.贵州医科大学临床微生物与免疫学教研室,贵阳 550001;5.江西中医药大
          学岐黄国医书院,南昌 330025)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)22-2740-05
          DOI  10.6039/j.issn.1001-0408.2023.22.09
          摘   要  目的  探讨异钩藤碱(IRN)调节单核细胞趋化蛋白1(MCP-1)/CC趋化因子受体2(CCR2)信号通路对哮喘小鼠气道炎症
          的影响。方法  通过注射和吸入卵清蛋白的方法建立哮喘小鼠模型,将造模成功后的小鼠随机分为哮喘组、IRN低剂量组(IRN-L
          组,灌胃10 mg/kg IRN)、IRN高剂量组(IRN-H组,灌胃20 mg/kg IRN)、IRN-H+CCL2组[灌胃20 mg/kg IRN+腹腔注射7.5 ng CC趋
          化因子配体(CCL2)]、阳性对照组(腹腔注射2 mg/kg地塞米松),并以注射和吸入无菌磷酸盐缓冲液的小鼠为空白对照组,每组10
          只。各药物组小鼠每天给予相应药物1次,连续给药2周。检测各组小鼠气道高反应指标——呼吸间歇(Penh)值,血清中肿瘤坏
          死因子 α(TNF-α)、白细胞介素 13(IL-13)、IL-4 水平,支气管肺泡灌洗液中嗜酸性粒细胞(EOS)、淋巴细胞(LYM)和中性粒细胞
         (NEU)数量,肺组织中 MCP-1、CCR2 蛋白表达水平;观察肺组织病理学变化并进行炎症细胞浸润评分。结果  与空白对照组比
          较,哮喘组小鼠肺组织炎症细胞浸润较明显,并有细胞肿胀、脱落现象发生;炎症细胞浸润评分,Penh值,IL-4、IL-13、TNF-α水平,
          EOS、NEU、LYM数量和MCP-1、CCR2蛋白表达水平均显著增加或升高(P<0.05);与哮喘组比较,IRN-L组、IRN-H组、阳性对照
          组小鼠肺组织病理损伤得到改善,上述定量指标均显著降低(P<0.05);与IRN-L组比较,IRN-H组、阳性对照组上述定量指标均
          显著降低(P<0.05);IRN-H组与阳性对照组比较,上述定量指标差异均无统计学意义(P>0.05);与IRN-H组比较,IRN-H+CCL2
          组上述定量指标均显著增加或升高(P<0.05),CCL2逆转了高剂量IRN对哮喘小鼠的保护作用。结论  IRN可能通过抑制MCP-1/
          CCR2信号通路的激活来减少哮喘小鼠气道炎症因子的释放,从而达到改善哮喘的目的。
          关键词  异钩藤碱;哮喘;单核细胞趋化蛋白1/CC趋化因子受体2信号通路;气道炎症

          Impacts of isorhynchophylline on airway inflammation in asthmatic mice
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          CAI Jin ,HUA Zhaozhao ,ZHANG Changrong ,HUANG Dan ,ZHANG Qihua ,WANG Yi ,ZHOU Sufang ,
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          LIU Lian ,GONG An (1.  Dept.  of  Classic  TCM,  the  First  Affiliated  Hospital  of  Guizhou  University  of
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          Traditional Chinese Medicine, Guiyang 550001, China;2. Dept. of Obstetrics, the Second Affiliated Hospital of
          Guizhou  University  of  Traditional  Chinese  Medicine,  Guiyang  550002,  China;3.  Research  Center  of
          Microecology,  Guizhou  University  of  Traditional  Chinese  Medicine,  Guiyang  550001,  China;4.  Clinical
          Microbiology  and  Immunology  Teaching  and  Research  Office,  Guizhou  Medical  University,  Guiyang  550001,
          China;5.  Qihuang  Academy  of  Traditional  Chinese  Medicine,  Jiangxi  University  of  Traditional  Chinese
          Medicine, Nanchang 330025, China)
          ABSTRACT    OBJECTIVE To investigate the impacts of isorhynchophylline (IRN) on airway inflammation in asthmatic mice by
          regulating  the  monocyte  chemotactic  protein-1 (MCP-1)/CC  chemokine  receptor  2 (CCR2)  signaling  pathway.  METHODS  The
          asthmatic mice model was established by injecting and inhaling ovalbumin. The successfully modeled mice were randomly grouped
          into  asthma  group,  IRN  low-dose  group (IRN-L,  intragastric  administration  of  10  mg/kg  IRN),  IRN  high-dose  group (IRN-H,
          intragastric  administration  of  20  mg/kg  IRN),  IRN-H+CCL2  group  [intragastric  administration  of  20  mg/kg  IRN+intraperitoneal
          injection  of  7.5  ng  CC  chemokine  ligand  2 (CCL2)]  and  positive  control  group (intraperitoneal  injection  of  2  mg/kg
          dexamethasone).  The  mice  injected  and  inhaled  with  sterile  phosphate-buffered  solution  were  included  in  the  blank  control  group,
          with 10 mice in each group. The mice in administration groups were given relevant medicine once a day, for consecutive 2 weeks.
                                                              The  levels  of  airway  hyperreactivity  indexes  such  as  enhanced
              Δ 基金项目 贵州省中医药管理局中医药、民族医药科学技术研
                                                              pause (Penh)  value,  tumor  necrosis  factor- α (TNF- α),
          究课题(No.QZYY-2023-038);贵州省卫生健康委科学技术基金项目
                                                              interleukin-13 (IL-13)  and  IL-4  in  serum,  the  number  of
         (No.gzwkj2023-139)
             *第一作者 主治医师,硕士。研究方向:内科杂病的中医药治疗                    eosinophil  (EOS) ,  lymphocyte  (LYM)  and  neutrophils
          和干预。E-mail:277787161@qq.com                        (NEU)  in  alveolar  lavage  fluid  and  the  protein  expressions  of
              # 通信作者 讲师,硕士。研究方向:中医药诊治内科杂病。                    MCP-1 and CCR2 in lung tissue were observed in each group;
          E-mail:307357997@qq.com                             the  pulmonary  histopathological  changes  were  observed,  and


          · 2740 ·    China Pharmacy  2023 Vol. 34  No. 22                            中国药房  2023年第34卷第22期
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