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枸地氯雷他定对小鼠过敏性肺炎的改善作用及机制
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          彭文娟 ,赵 炎 ,岳少云 ,吴玉娇 ,莫佳佳 ,储昭兴 (1.安徽省胸科医院内三科,合肥 230022;2.合肥医工
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          医药股份有限公司,合肥 230601)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)15-1882-05
          DOI  10.6039/j.issn.1001-0408.2025.15.11
          摘   要  目的  探讨枸地氯雷他定对小鼠过敏性肺炎(HP)的改善作用及机制。方法  将60只小鼠按随机数字表法分为空白对照
          组(生理盐水)、模型组(生理盐水)、泼尼松组(阳性对照,20 mg/kg)和枸地氯雷他定低、中、高剂量组(0.5、1、2 mg/kg),每组10只。
          除空白对照组外,其余各组小鼠均通过腹腔注射卵清蛋白和吸入卵清蛋白喷雾构建HP模型。从造模第22天开始,各组小鼠灌胃
          相应药物/生理盐水,每天1次,连续11 d。末次给药后,评估各组小鼠肺功能和气道高反应性,检测血清中白细胞介素(IL)-1β、IL-
          4、IL-6水平和支气管肺泡灌洗液中IL-8、IL-13、IL-17A水平,观察各组小鼠肺组织Masson染色病理变化,检测肺组织中纤维化相
          关蛋白转化生长因子β1 (TGF-β1 )、3型胶原蛋白(Col-Ⅲ)和纤维连接蛋白(FN)的表达。结果  与空白对照组比较,模型组小鼠肺
          功能显著降低(P<0.01),气道阻力和血清中IL-1β、IL-4、IL-6水平以及支气管肺泡灌洗液中IL-8、IL-13、IL-17A水平均显著升高
         (P<0.01);肺组织出现肺泡塌陷、萎缩及结构紊乱,并生成大量蓝色胶原纤维沉积,阳性染色百分比显著升高(P<0.01);肺组织
          中TGF-β1、Col-Ⅲ和FN蛋白表达水平均显著升高(P<0.01)。给予枸地氯雷他定干预后,枸地氯雷他定各剂量组小鼠肺组织病理
          变化均有不同程度改善,以上指标水平大部分显著逆转(P<0.05或P<0.01)。结论  枸地氯雷他定可改善HP小鼠的肺功能和气
          道高反应性,抑制血清和支气管肺泡灌洗液中炎症因子的释放,降低胶原纤维的沉积,其作用机制可能与抗炎、调节免疫和抗纤维
          化相关。
          关键词  枸地氯雷他定;过敏性肺炎;肺功能;抗炎;纤维化


          Improvement  effect  and  mechanism  of  desloratadine  citrate  disodium  in  hypersensitivity  pneumonitis
          model mice
          PENG Wenjuan ,ZHAO Yan ,YUE Shaoyun ,WU Yujiao ,MO Jiajia ,CHU Zhaoxing(1.  Dept.  of  Internal
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          Medicine  Ⅲ ,  Anhui  Chest  Hospital,  Hefei  230022,  China;2.  Hefei  Industrial  Pharmaceutical  Institute  Co.,
          Ltd., Hefei 230601, China)
          ABSTRACT    OBJECTIVE  To  investigate  the  improvement  effect  and  mechanism  of  desloratadine  citrate  disodium  in  mice  with
          hypersensitivity  pneumonitis (HP).  METHODS  Sixty  mice  were  randomly  divided  into  blank  control  group (normal  saline),
          model  group (normal  saline),  prednisone  group (positive  control,  20  mg/kg)  and  desloratadine  citrate  disodium  low-,  medium-
          and  high-dose  groups (0.5,  1,  2  mg/kg),  with  10  mice  in  each  group.  Except  for  the  blank  control  group,  mice  in  other  groups
          were  intraperitoneally  injected  with  ovalbumin (OVA)  and  exposed  to  OVA  inhalation  to  establish  the  HP  model.  On  day  22  post-
          modeling,  mice  in  each  group  were  administered  the  corresponding  drugs  or  normal  saline,  once  a  day,  for  11  consecutive  days.
          After  the  last  administration,  lung  function  and  airway  hyperreactivity  were  assessed.  The  levels  of  interleukin-1β (IL-1β),  IL-4
          and  IL-6  in  serum  as  well  as  the  levels  of  IL-8,  IL-13  and  IL-17A  in  bronchoalveolar  lavage  fluid  were  determined.  Pathological
          changes  in  lung  tissue  of  mice  were  evaluated  using  Masson  staining.  Furthermore,  the  expressions  of  fibrosis-related  proteins,
          including  transforming  growth  factor  β1 (TGF- β1 ),  type  Ⅲ  collagen (Col- Ⅲ)  and  fibronectin (FN)  were  determined  in  lung
          tissues. RESULTS Compared with the blank control group, the model group showed significant deterioration in lung function (P<
          0.01),  while  airway  resistance  and  serum  levels  of  IL-1β,  IL-4,  IL-6  and  the  levels  of  IL-8,  IL-13  and  IL-17A  in  the
          bronchoalveolar  lavage  fluid  were  increased  significantly (P<0.01).  The  lung  tissues  exhibited  alveolar  collapse,  atrophy,  and
          structural  disarray,  along  with  the  formation  of  extensive  deposits  of  blue  collagen  fibers,  the  percentage  of  positive  staining
                                                              increased  significantly (P<0.01). Additionally,  the  expression
              Δ 基金项目 安徽省科技重大专项(No.202203a07020029)            levels of TGF-β1, Col-Ⅲ, and FN proteins in the lung tissues
             *第一作者 副主任医师。研究方向:呼吸康复、呼吸系统临床药
                                                              were  also  increased  significantly (P<0.01). After  intervention
          物应用。E-mail:pengwenjuan1983@sina.com
              # 通信作者 主任药师,博士。研究方向:创新药物研发、分子药理                 with  desloratadine  citrate  disodium,  the  pathological  changes
          学。E-mail:chuzhaoxing@163.com                        in  the  lung  tissues  of  mice  in  each  dosage  group  of


          · 1882 ·    China Pharmacy  2025 Vol. 36  No. 15                            中国药房  2025年第36卷第15期
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