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吴茱萸碱对哮喘模型大鼠炎症及上皮细胞凋亡的影响及机制
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          雷 俊 ，卢丽君 ，罗玲艳 ，乔 松 ，童亚男 ，郑 洋 ，姚 蕾 [1.武汉市中医医院肺系病科，武汉 430014；
          2.武汉市第三医院（武汉大学附属同仁医院）急诊医学科，武汉 430014]
          中图分类号  R965；R285.5      文献标志码  A      文章编号  1001-0408（2024）11-1351-06
          DOI  10.6039/j.issn.1001-0408.2024.11.12
          摘  要  目的  探究吴茱萸碱对哮喘模型大鼠炎症反应及上皮细胞凋亡的影响及潜在机制。方法  将SD大鼠分为对照组、模型
          组、吴茱萸碱低剂量组（10 mg/kg）、吴茱萸碱高剂量组（20 mg/kg）、地塞米松组（阳性对照，0.5 mg/kg）、表皮细胞生长因子（EGF）组
          [丝裂原活化蛋白激酶（MAPK）激活剂，10 μg]、吴茱萸碱高剂量+EGF组（20 mg/kg吴茱萸碱+10 μg EGF），每组10只。除对照组
          外，其余各组大鼠以10%卵白蛋白（OVA）-氢氧化铝混合液3点注射致敏联合2%OVA雾化液吸入激发的方式建立哮喘模型。检
          测各组大鼠支气管肺泡灌洗液（BALF）中的炎症细胞（巨噬细胞、淋巴细胞）数，观察大鼠肺组织的病理变化，检测大鼠肺组织中气
          道上皮细胞凋亡情况、血清炎症因子（肿瘤坏死因子α、白细胞介素6、白细胞介素4）水平、通路相关蛋白[p38 MAPK、磷酸化p38
          MAPK（p-p38 MAPK）、信号转导及转录激活因子1（STAT1）]及凋亡相关蛋白[B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）]的
          表达水平。结果  与对照组比较，模型组大鼠肺组织可见支气管黏膜水肿、肺泡间隔增厚和大量炎症细胞浸润，炎症细胞数显著增
          多；气道上皮细胞凋亡率、炎症因子水平、p-38 MAPK/p-38 MAPK和Bax、STAT1蛋白表达水平均显著升高，Bcl-2蛋白表达水平和
          Bcl-2/Bax均显著降低（P＜0.05）。与模型组比较，吴茱萸碱低、高剂量组和地塞米松组大鼠肺组织病理改变均有不同程度缓解，上
          述各指标均显著逆转，而EGF组上述指标的变化趋势则相反（P＜0.05）；EGF能显著减弱高剂量吴茱萸碱对哮喘大鼠炎症反应的
          改善作用（P＜0.05）。结论  吴茱萸碱可减轻哮喘大鼠炎症反应并减少气道上皮细胞凋亡，其作用机制可能与抑制 p38 MAPK/
          STAT1信号通路有关。
          关键词  吴茱萸碱；哮喘；炎症反应；气道上皮细胞；凋亡；p38 MAPK/STAT1信号通路

          Effects of evodiamine on inflammation and apoptosis of airway epithelial cells in asthma model rats and its
          mechanism
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          LEI Jun ，LU Lijun ，LUO Lingyan ，QIAO Song ，TONG Yanan ，ZHENG Yang ，YAO Lei [1.  Dept.  of
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          Pulmonary  Diseases，  Wuhan  Hospital  of  Traditional  Chinese  Medicine，  Wuhan  430014，  China；2.  Dept.  of
          Emergency Medicine， Wuhan Third Hospital （Tongren Hospital of Wuhan University）， Wuhan 430014， China]
          ABSTRACT   OBJECTIVE  To  explore  the  effects  and  potential  mechanism  of  evodiamine  on  inflammatory  response  and
          apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine
          low-dose  group （10  mg/kg），  evodiamine  high-dose  group （20  mg/kg），  dexamethasone  group （positive  control，  0.5  mg/kg），
          epidermal  growth  factor （EGF）  group  [mitogen-activated  protein  kinase （MAPK）  activator，  10  μg]，  evodiamine  high-dose+EGF
          group （20  mg/kg  evodiamine+10  μg  EGF），  with  10  rats  in  each  group.  Except  for  the  control  group，  the  other  groups  were
          sensitized  by  3-point  injection  of  10%  ovalbumin（OVA）-aluminium  hydroxide  mixture  and  stimulated  by  inhalation  of  2%OVA
          nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar
          lavage  fluid （BALF）  was  detected  in  each  group；  pathological  changes  of  lung  tissue  in  rats  were  observed；  the  apoptosis  of
          airway  epithelial  cells，  the  levels  of  serum  inflammatory  factors  [tumor  necrosis  factor- α，  interleukin-6 （IL-6）  and  IL-4]，  the
          expressions  of  pathway-related  proteins  p38  MAPK，  phosphorylated  p38  MAPK （p-p38  MAPK），  signal  transduction  and
          transcription  activating  factor  1 （STAT1）]  and  apoptosis-related  proteins  [B  cell  lymphoma-2 （Bcl-2）  and  Bcl-2  associated  X
          protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening
          of  alveolar  septa  and  extensive  infiltration  of  inflammatory  cells  were  observed  in  the  lung  tissue  of  rats  in  the  model  group；  the
          number  of  inflammatory  cells，  apoptosis  rate  of  airway  epithelial  cells，  the  levels  of  inflammatory  factors，  p-38  MAPK/p-38
          MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax
          were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to
          varying  degrees  in  evodiamine  low-dose  and  high-dose  groups，  and  dexamethasone  groups，  and  the  above  indicators  were
                                                             significantly  reversed.  However，  the  change  trends  of

             Δ 基金项目 武汉市医学科研项目（No.WZ21C57）                    corresponding  indicators  in  the  EGF  group  were  opposite  to
             ＊第一作者 主治医师，硕士。研究方向：中医药防治呼吸系统疾                   the  above （P＜0.05）.  EGF  could  significantly  attenuate  the
          病。E-mail：leijlj@163.com                            effect  of  high-dose  evodiamine  on  inflammatory  response  in
             # 通信作者 副主任医师，硕士。研究方向：中医药防治呼吸系统                  asthmatic  rats （P＜0.05）.  CONCLUSIONS  Evodiamine  can
          疾病。E-mail：xiah46581@163.com                        relieve  inflammatory  reactions  and  inhibit  the  apoptosis  of


          中国药房  2024年第35卷第11期                                              China Pharmacy  2024 Vol. 35  No. 11    · 1351 ·
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