冬菀止咳颗粒对咳嗽变异性哮喘大鼠TLR4/MyD88/NF-κB信号通路的影响  

Effect of Dongwan Zhike granules on TLR4/MyD88/NF-κB signaling pathway in rats with cough variant asthma

作　　者：张静文 李颖萌 熊艳霞 王丽华[3] 吴样明 詹扬 ZHANG Jing-wen;LI Ying-meng;XIONG Yan-xia;WANG Li-hua;WU Yang-ming;ZHAN Yang(State Key Laboratory for the Modernization of Classical Prescriptions of ChineseMedicine,Nanchang 330103;Jiangzhong Pharmaceutical Co.,Ltd.,Nanchang 330103;Department of Pulmonary Diseases,Affiliated Hospital of Jiangxi University of Traditional ChineseMedicine,Nanchang 330103)

机构地区：[1]经典名方现代中药创制全国重点实验室,南昌330103 [2]江中药业股份有限公司,南昌330103 [3]江西中医药大学附属医院肺病科,南昌330103

出　　处：《中南药学》2025年第2期455-460,共6页Central South Pharmacy

基　　金：经典名方研发与国际拓展研究项目(No.20232BBH80009);冬菀止咳颗粒工艺改进和标准提升研究(No.2019A161);江西省重点研发计划项目(No.20243BBI91016)。

摘　　要：目的通过建立咳嗽变异性哮喘(CVA)模型,基于TLR4/MyD88/NF-κB通路考察冬菀止咳颗粒对该哮喘模型的改善作用及初步的作用机制。方法给药14 d后测定各组动物呼吸功能指标、咳嗽次数及血清IL-4、IgE含量,计算肺脏系数,检测肺泡灌洗液中白细胞总数和炎性细胞分类数,观察各组肺脏组织病理学切片,Western blot法检测大鼠肺组织中TLR4、MyD88、p-p65的蛋白表达水平。结果与空白组相比,给药第14日后模型组动物呼吸功能指标吸气时间(TI)、潮气量(TV)、松弛时间(RT)、每分钟吸气量(MV)、呼吸频率(F)均显著降低,气道狭窄指数(Penh)显著升高(P<0.05或P<0.01),模型组动物咳嗽次数、肺脏系数、白细胞(WBC)、单核细胞(MONO)、淋巴细胞(LYMPH)、嗜酸性粒细胞(EO)、免疫球蛋白E(IgE)、白细胞介素4(IL-4)水平均显著升高(P<0.05或P<0.01)。与模型组相比,冬菀止咳颗粒可改善呼吸功能指标,降低咳嗽次数、肺脏系数、肺泡灌洗液中白细胞总数和细胞分类数及血清中IgE、IL-4水平(P<0.05或P<0.01)。Western blot结果表明,与空白组相比,模型组中TLR4、MyD88、p-p65的蛋白表达显著升高(P<0.01);与模型组相比,冬菀止咳颗粒组及醋酸地塞米松片组TLR4、MyD88、p-p65的蛋白表达显著降低(P<0.05或P<0.01)。结论冬菀止咳颗粒在1.35、2.70、5.40 g·kg^(-1)剂量下对CVA大鼠模型具有一定的改善作用,可能与调控、降低气道炎症、TLR4/MyD88/NF-κB信号通路;改善呼吸功能有关。Objective To determine the effect of Dongwan Zhike granules on rats model with cough variant asthma(CVA)and its related mechanism based on TLR4/MyD88/NF-κB signaling pathway.Methods At 14 days after the administration,the respiratory function indexes,the serum IL-4 and IgE levels,the lung coefficient,white blood cells and inflammatory cells in the bronchoalveolar lavage fluid were measured,and the pathological sections observed.The protein expression levels of TLR4,MyD88 and p-p65 in the lung tissue were detected by Western blot.Results Compared with the blank group,the respiratory function indicators of the model group were significantly decreased in inspiratory time,tidal volume,relaxation time,inspiratory volume per minute,and respiratory rate,white airway stenosis index(Penh)was obviously increased(P<0.05 or P<0.01).The lung coefficient,white blood cells,monocytes,lymphocytes,eosinophils,immunoglobulin E and interleukin-4 levels in model rats were significantly increased(P<0.05 or P<0.01).Compared with the model group,Dongwan Zhike granule improved the respiratory function index,reduced the lung coefficient,the total number of white blood cells and cell types in the bronchoalveolar lavage fluid,and the levels of IgE and IL-4 in the serum(P<0.05 or P<0.01).Western blot showed that the protein expression of TLR4,MyD88 and p-p65 in the model group was much higher than that in the blank group(P<0.01).The protein expression of TLR4,MyD88,and p-p65 protein expression decreased in Dongwan Zhike granules and dexamethasone acetate groups(P<0.05 or P<0.01).Conclusion Dongwan Zhike granules at 1.35,2.70 and 5.40 g·kg^(-1) can improve the CVA in the rat model,which may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway to reduce the airway inflammation and improve the respiratory function.

关 键 词：咳嗽变异性哮喘 冬菀止咳颗粒 咳嗽 呼吸功能 气道炎症 

分 类 号：R285[医药卫生—中药学]