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21日起，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），表明模型组大鼠肺组织出现损伤。与模型组相比较，工艺1大剂量组及小剂量组FEV0.3/FVC%、MVV显著升高（P < 0.01），RL显著降低（P < 0.01）；工艺2大剂量组及小剂量组FEV0.3/FVC %、MVV均显著升高（P < 0.01），工艺2小剂量组Cdyn显著升高（P < 0.01），RL、Re、肺指数显著降低（P < 0.01或P < 0.05）。HE染色结果显示，与空白组相比，模型组大鼠气管可见大量炎症细胞浸润，气管纤毛脱落，呈现COPD病理状态。与模型组相比较，工艺1和工艺2大、小剂量组大鼠气管周围炎性细胞减少，肺间隔变小，COPD病理过程得到有效缓解。AB-PAS染色结果显示，与空白组相比较，模型组杯状细胞数目显著升高（P < 0.05）；与模型组相比较，工艺1大、小剂量组，工艺2大、小剂量组杯状细胞数目显著降低（P < 0.05）。通过肺功能、肺指数及杯状细胞数目数据结果分析，工艺2小剂量组比工艺1小剂量在Cdyn、Re、肺指数方面效果均更为明显；工艺2大剂量组与工艺1大剂量相比气道纤毛上杯状细胞数目减少得更为显著。结论 两种工艺的芪蛭益肺颗粒对COPD模型大鼠均有一定的治疗作用，但全方水提醇沉工艺得到的药物疗效更佳。

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^st day and the rats were kept away from smoke on these days. On the 21^st day 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^st day, all rats were given the specific drug by gavage once a day for 40 days. On the 61^st day, 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 the vehicle group, FEV0.3, FEV0.3/FVC%, FEV25-75%, PEF, MVV, Cdyn were significantly decreased (P < 0.01 or P <0.05) and RL were significantly increased (P < 0.05), indicating that the lung function of the model group was deceased severely. Lung index of the model group was increased notably (P < 0.05), indicating that the lungs were damaged. Compared with the model group, FEV0.3/FVC% and MVV were significantly increased and RL was significantly decreased in the Qizhi Yifei Granules process 1 group with high and low dose (P < 0.01). Compared with the model group, FEV0.3/FVC%, MVV was significantly increased in the Qizhi Yifei Granules process 2 groups with high and low dose (P<0.01), and Cdyn was significantly increased in the Qizhi Yifei Granules process 2 groups with low dose (P <0.01). RL and Re were significantly decreased in the Qizhi Yifei Granules process 2 groups with low dose (P < 0.01 or P < 0.05). HE staining result showed that compared with the vehicle group, a large number of inflammatory cells infiltrated in the trachea of the model group and the tracheal cilia fell off, showing the pathological state of COPD. Compared with the model group, the number of inflammatory cells around the trachea was decreased in the process 1 and the 2 groups, and the lung interval became smaller. The pathological process of COPD was effectively alleviated. AB-PAS staining showed that the number of goblet cells in the model group was significantly higher than that in the vehicle group (P < 0.05). Compared with the model group, the numbers of goblet cells in the process 1 and 2 groups were all significantly decreased (P < 0.05 or P < 0.05). According to the results of lung function, lung index, and the number of goblet cells, the effects of Cdyn, Re and lung index of process 2 with low dose were more obvious than those of process 1 with low dose. The number of goblet cells on the cilia was significantly decreased in the group of process 2 with high dose compared to the group of process 1 with high dose. Conclusion The two processes of Qizhi Yifei granule have a certain therapeutic effect on COPD model rats and the drug obtained by alcohol extracting-water precipitation is more effective.

R285.5