目的 基于 MAPK/NF-κB 信号通路探讨调气止咳方（麻黄、苦杏仁、浙贝母、黄芩、瓜蒌子等）对咳嗽 变异性哮喘大鼠气道炎症的影响及机制。方法 采用卵清蛋白致敏复制咳嗽变异性哮喘大鼠模型。将 SD 大鼠 随机分组为空白组、模型组、地塞米松组（0.5 mg·kg-1）、孟鲁司特组（1.0 mg·kg-1）及调气止咳方低、中、高剂 量组（9.6、19.2、38.4 g·kg-1），每组 10 只；灌胃给药，每日 1 次，连续 14 d。观察大鼠一般状况并记录雾 化后 2 min 内大鼠的咳嗽次数；采用 HE 染色、Masson 染色法观察大鼠肺组织病理变化；ELISA 法检测血清白 细胞介素 1β（IL-1β）、IL-6、肿瘤坏死因子 α（TNF-α）含量；Western Blot 法检测肺组织 p38 MAPK、p-p38、 NF-κB p65、p-p65 蛋白表达水平；RT-qPCR 法检测肺组织 p38 MAPK、NF-κB p65 mRNA 表达水平。结果 与空白组比较，模型组大鼠的咳嗽次数显著增加（P＜0.01），肺损伤病理评分及胶原纤维面积比显著升高（P＜ 0.01）；血清 IL-1β、IL-6、TNF-α 水平均显著升高（P＜0.01）；肺组织中 p-p38、p-p65、p-p38/p38、p-p65/ p65 蛋白表达均显著上调（P＜0.01），p38 MAPK、NF-κB p65 mRNA 表达显著上调（P＜0.01）。与模型组比较， 各给药组大鼠的咳嗽次数显著减少（P＜0.01），肺损伤病理评分及胶原纤维面积比显著降低（P＜0.01），血清 IL-1β、IL-6、TNF-α 水平均显著降低（P＜0.01），肺组织中 p-p38、p-p65 蛋白表达及 p38 MAPK、NF-κB p65 mRNA 表达均明显下调（P＜0.05，P＜0.01）；调气止咳方高剂量组大鼠肺组织中 p-p38/p38、p-p65/p65 蛋 白表达比值均显著下调（P＜0.01）。与地塞米松组和孟鲁司特组比较，调气止咳方高剂量组大鼠的咳嗽次数明 显减少（P＜0.05）；与地塞米松组比较，调气止咳方高剂量组大鼠的血清 IL-1β、IL-6、TNF-α 水平明显降低 （P＜0.01）；与孟鲁司特组比较，调气止咳方高剂量组大鼠的血清 IL-1β、TNF-α 水平明显降低（P＜0.05， P＜0.01）。结论 调气止咳方能够改善卵清蛋白诱导的咳嗽变异性哮喘大鼠的咳嗽症状，减轻气道炎症细胞 浸润及气道重塑，降低炎症细胞因子 IL-1β、IL-6、TNF-α 水平，其机制可能与调控 MAPK/NF-κB 信号通路 有关。

Objective To investigate the effects and mechanisms of Tiaoqi Zhike Prescription （Ephedrae Herba， Armeniacae Semen Amarum， Fritillariae Thunbergii Bulbus， Scutellariae Radix， Trichosanthis Semen， etc.） on airway inflammation in cough variant asthma rats based on the MAPK/NF- κB signaling pathway. Methods Cough variant asthma rat model was established by ovalbumin sensitization. SD rats were randomly divided into blank group， model group，Dexamethasone group （0.5 mg·kg-1），Montelukast group （1.0 mg·kg-1）and Tiaoqi Zhike Prescription low- ， medium- and high- dose groups （9.6， 19.2， 38.4 g·kg-1）， with 10 rats in each group. Intragastric administration was given once a day for 14 consecutive days. The general condition of rats was observed and the number of coughs in rats within two minutes after atomization was recorded. HE staining and Masson staining were used to observe the pathological changes of lung tissue in rats. The levels of serum interleukin-1β （IL-1β），IL-6 and tumor necrosis factor- α （TNF- α） were detected by ELISA. The protein expression levels of p38 MAPK， p-p38， NF- κB p65 and p-p65 in lung tissue were detected by Western Blot. The mRNA expression levels of p38 MAPK and NF- κB p65 in lung tissue were detected by RT-qPCR. Results Compared with the blank group， the times of coughs in the model group was significantly increased （P＜0.01），and the pathological score of lung injury and the area ratio of collagen fibers were significantly increased （P＜0.01）. The levels of serum IL-1β，IL-6 and TNF-α were significantly increased （P＜0.01） . The protein expressions of p-p38，p-p65，p-p38/p38 and pp65/p65 in lung tissue were significantly up-regulated （P＜0.01），and the mRNA expressions of p38 MAPK and NF- κB p65 were significantly up-regulated （P＜0.01）. Compared with the model group，the cough frequency of rats in each administration group was significantly decreased （P＜0.01），the pathological score of lung injury and the area ratio of collagen fibers were significantly decreased （P＜0.01），the levels of serum IL-1β，IL-6 and TNF-α were significantly decreased （P＜0.01）， and the protein expressions of p-p38 and p-p65 and the mRNA expressions of p38 MAPK and NF-κB p65 in lung tissue were significantly down-regulated （P＜0.05，P＜0.01）. The protein expression ratios of p-p3/p38 and p-p65/p65 in the lung tissue of rats in the high-dose group of Tiaoqi Zhike Prescription were significantly down-regulated （P＜0.01） . Compared with the Dexamethasone group and the Montelukast group， the number of coughs in the high-dose group of Tiaoqi Zhike Prescription was significantly reduced （P＜0.05）. Compared with the Dexamethasone group，the serum levels of IL-1β，IL-6 and TNF-α in the high-dose group of Tiaoqi Zhike Prescription were significantly decreased （P＜0.01）. Compared with the Montelukast group，the levels of serum IL-1β and TNF-α in the high-dose group of Tiaoqi Zhike Prescription were significantly decreased （P＜0.05， P＜0.01）. Conclusion Tiaoqi Zhike Prescription can improve the cough symptoms of ovalbumin-induced cough variant asthma model rats，reduce airway inflammatory cell infiltration and airway remodeling，and reduce the levels of inflammatory cytokines IL-1β，IL-6 and TNF-α. The mechanism may be related to the regulation of MAPK/NF-κB signaling pathway.

R285.5

国家自然科学基金项目（82274500）；安徽省教育厅高校自然科学项目（KJ2020A0425）；王胜安徽省名中医工作室项目。