止喘灵注射液雾化给药对过敏性支气管哮喘小鼠模型的治疗作用及安全性评价  

Efficacy and safety evaluation of aerosol inhalation of Zhichuanling injection on bronchial asthma

作　　者：牛博 吴晗禹 赵芳 曹征宇 NIU Bo;WU Hanyu;ZHAO Fang;CAO Zhengyu(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院,江苏南京211198

出　　处：《山东第一医科大学（山东省医学科学院）学报》2022年第11期805-813,共9页Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences

基　　金：国家自然科学基金(21777192,81903826,82100585,82204653);“双一流”高校建设专项资金(CPU2018GF06);江苏省自然科学基金(BK20221054);中央高校基本科研业务费(2632022PY07)。

摘　　要：目的探讨止喘灵注射液雾化给药对卵清蛋白(ovalbumin,OVA)诱导的小鼠过敏性支气管哮喘的治疗效果,评价止喘灵注射液雾化吸入给药的安全性。方法通过检测小鼠哮喘的潜伏期和哮喘次数评价哮喘症状的严重程度;通过HE染色观察肺组织病理变化;通过全自动血液分析仪检测支气管肺泡灌洗液中白细胞总数(white blood cell,WBC)、嗜酸性粒细胞(eosinophil,Eos)、淋巴细胞(lymphocyte,Lym)和中性粒细胞(neutrophil,Neu)的数目评价过敏性炎症反应;通过酶联免疫吸附法测定血清中白介素⁃4(interleukin⁃4,IL⁃4)、免疫球蛋白E(immunoglobulin E,IgE)的表达量;通过观察动物一般行为、神经系统反应评价大剂量连续雾化给予止喘灵注射液的安全性。结果雾化吸入不同浓度止喘灵注射液可缓解小鼠哮喘样行为、改善肺组织病理变化、降低支气管肺泡灌洗液中炎症细胞数目及血液中IL⁃4、IgE表达量。其中以止喘灵注射液稀释1倍(临床剂量)效果最佳,与阳性对照药布地奈德效果相当。雾化吸入相当于20倍临床剂量止喘灵注射液对小鼠一般行为、神经系统、尿液、粪便、唾液、体质量以及摄食量无影响。结论雾化吸入止喘灵注射液是一种安全、有效的治疗小鼠过敏性支气管哮喘的给药方式。Objective:To explore the therapeutic efficacy of nebulized administration of Zhichuanling injection on allergic bronchial asthma in mice induced by ovalbumin(OVA),and to investigate the safety of high-dose nebulization of Zhichuanling injection.Methods:Animal welfare and experimental procedures followed the regulations of the Ethics Committee of China Pharmaceutical University.The severity of asthma symptoms was assessed by quantification of the latency and frequency of asthma-like behavior in mice.H&E staining was used to investigate histopathological changes in the lung.The total number of white blood cells(WBC),eosinophil(Eos),lymphocyte(Lym)and neutrophils(Neu)in bronchoalveolar lavage fluid were measured by automatic hematology analyzer to evaluate the allergic inflammatory response.Serum levels of interleukin-4(IL-4)and immunoglobulin E(IgE)were quantified using ELISA.The safety of high-dose nebulization of Zhichuanlin injection was evaluated by examining the general behavior and nervous system response of animals.Results:Our data demonstrated that the nebulized inhalation of different concentrations of Zhichuanling injection alleviated the asthma-like behavior of mice,improved the pathology of lung tissue,reduced the number of inflammatory cells in bronchoalveolar lavage fluid and the levels of IL-4 and IgG in the blood.Among the doses tested,the 1:1 dilution of Zhichuanling injection(the clinic dose)displayed the best efficacy that was comparable to the positive control,budesonide.Nebulized inhalation of a high dose(20×clinic dose)Zhichuanling injection did not affect the general behavior,nervous and autonomic nervous system,urine,feces,saliva,body weight and food intake of mice.Conclusion:Considering these data together,nebulized inhalation of Zhichuanling injection may represent an effective and safe drug administration route for bronchial asthma treatment.

关 键 词：止喘灵注射液 支气管哮喘 雾化吸入 药效 安全性 

分 类 号：R285.5[医药卫生—中药学]