摘要
目的本实验利用烟熏复合气道滴注LPS的方法复制大鼠COPD模型,通过对COPD模型大鼠肺组织形态学及肺功能的测定,比较全方水提(工艺1)和全方水提醇沉工艺(工艺2)的芪蛭益肺颗粒对COPD模型大鼠的影响,从而筛选出药效学作用更佳的制备工艺,为新药开发提供依据。方法 Wistar大鼠126只,其中空白组23只,造模大鼠103只。使用自制烟熏箱烟熏大鼠,持续烟熏28 d;于第1、11、21 d气道内滴注LPS,滴药日不熏烟。实验第21 d分别从空白组及造模组中各取7只雄性大鼠测定肺功能各指标:最大通气量(MVV)、用力呼气容积(FVC)、用力呼气流速(FEV25-75%)、第0.3 s用力呼气容积与用力呼气容积百分比(FEV0.3/FVC%),进行给药前模型复制成功鉴定。将剩余造模大鼠随机分为模型组、罗红霉素组(0.03 g·kg^-1)、工艺1大剂量组(临床等效剂量,9.10 g·kg^-1)、工艺1小剂量组(1/2临床等效剂量,4.55 g·kg^-1)、工艺2大剂量组(临床等效剂量,9.10 g·kg^-1)、工艺2小剂量组(1/2临床等效剂量,4.55 g·kg^-1),每组16只,雌雄各半。实验第21d起,各组大鼠每日灌胃给予相应药物1次,连续给药40 d。实验第61 d测定大鼠肺功能各指标:FVC、FEV0.3/FVC%、FEV25-75%、MVV、第0.3 s用力呼气容积(FEV0.3)、用力最大呼气流速(PEF)、吸气总阻力(RL)、呼气总阻力(Re)、动态顺应性(Cdyn)、肺指数,通过HE及AB-PAS染色观察肺组织形态结构和气道纤毛上杯状细胞数目。结果给药前模型复制成功鉴定实验中肺功能测定结果显示,与空白组相比较,模型组大鼠MVV、FVC、FEV25-75%、FEV0.3/FVC%均显著降低(P <0.05),表明COPD大鼠模型复制成功。给药后(实验第61 d)肺功能测定结果显示,与空白组相比较,模型组FEV0.3、FEV0.3/FVC%、FEF25-75%、PEF、MVV、Cdyn均显著降低(P <0.01或P <0.05),RL显著升高(P <0.05),表明模型组大鼠肺功能出现严重降低;模型组肺指数显著升高(P <0.05),表明模型组大�
Objective A rat model of COPD was established by infusion of LPS with cigarette smoke exposure. The aim of this experiment is to compare the effect of Qizhi Yifei granules on COPD model rats with aqueous extract(process 1)and alcohol extracting-water precipitation(process 2) and to screen out the preparation techniques with better pharmacodynamics effects by detecting the changes of lungs and lung function, to provide basis for new drug development. Methods There were 126 Wistar rats in this experiment with 23 rats in a vehicle group and another 103 rats in a model group. COPD rats were exposed to smoke in a homemade smoking box for 28 days. Drop LPS in the airways on the 1 st, 11 th, and 21 stday and the rats were kept away from smoke on these days. On the 21 stday of experiment, 7 male rats were randomly taken from the vehicle group and the model group respectively to determine maximum ventilation(MVV), forced vital capacity(FVC), forced expiratory flow rate(FEV25-75%), FEV0.3/FVC% for pre-dose model identification. The rest of model rats were randomly divided into a model group, a roxithromycin group, two groups of Qizhi Yifei granules process 1 with high(9.10 g·kg^-1) and low(4.55 g·kg^-1) dosage and two groups of Qizhi Yifei Granules process 2 with high(9.10 g·kg^-1) and low(4.55 g·kg^-1) dosage. Each group had 16 rats with half male and half female. From the 21 stday, all rats were given the specific drug by gavage once a day for 40 days. On the 61 stday, all rats were sacrificed to determine FVC, FEV0.3/FVC%, FEV25-75%, MVV, 0.3% forced expiratory volume(FEV0.3),maximum forced expiratory flow rate(PEF) and forced vital capacity(RL), total exhalation resistance(Re), dynamic compliance(Cdyn), lung index. The lungs and the number of tracheal epithelia goblet cells in each group were subjected to HE and AB-PAS staining. Results Compared with the model group, MVV, FVC, FEV25-75%, FEV0.3/FVC% were significantly decreased(P < 0.05), indicating that COPD model rats were duplicated successfully. Compared with t
作者
李嘉萌
杨容芳
余丰君
冯淬灵
王晶
Li Jiameng;Yang Rongfang;Yu Fengjun;Feng Cuiling;Wang Jing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China;Peking University People's Hospital,Beijing 100044,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2019年第11期2428-2435,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
北京市科学技术委员会“G20工程支撑保障十病十药研发”项目(Z151100003815018):芪蛭益肺颗粒治疗慢性阻塞性肺疾病稳定期的成药性研究,负责人:冯淬灵。
关键词
芪蛭益肺颗粒
慢性阻塞性肺疾病
工艺筛选
Qizhi Yifei granules
Chronic obstructive pulmonary disease
Process screening
