风咳汤通过SIRT1/NF-κB/NLRP3信号通路减轻咳嗽变异性哮喘大鼠气道炎症  

Fengke decoction alleviates trachea inflammation in cough variant asthma rats via SIRT1/NF-κB/NLRP3 signaling pathway

作　　者：王超 唐鸿 王东旭[1] 陈磊垚[1] 王勇[1] 袁亮亮[1] 翟慧媛 WANG Chao;TANG Hong;WANG Dong-xu;CHEN Lei-yao;WANG Yong;YUAN Liang-liang;ZHAI Hui-yuan(Nanjing Integrated Traditional Chinese and Western Medicine Hospital,Nanjing 210014;Jiangsu Health Vocational College,Nanjing 210029)

机构地区：[1]南京市中西医结合医院,南京210014 [2]江苏卫生健康职业学院,南京210029

出　　处：《中南药学》2024年第10期2576-2582,共7页Central South Pharmacy

基　　金：南京市医学科技发展项目(No.YKK17191);江苏省中医药管理局中医药科技发展计划项目(No.YB2020034);2023年江苏省中药骨干人才项目;2024年市级老药工传承工作室;江苏卫生健康职业学院校级科研项目(No.JKCY202417)。

摘　　要：目的探讨风咳汤对咳嗽变异性哮喘(CVA)大鼠气道炎症及肺功能的改善作用及机制。方法采用卵蛋白(OVA)和氢氧化铝混合物1 mL皮下注射致敏后再以雾化的OVA激发哮喘建立CVA大鼠模型,分别给予风咳汤低剂量、高剂量和地塞米松进行治疗,正常对照组与模型组灌胃相应体积生理盐水。Diff-Quick法进行肺泡灌洗液(BALF)中炎症细胞计数,ELISA法检测各组大鼠BALF上清液中白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、白细胞介素-17(IL-17)、白细胞介素-22(IL-22)含量;观察大鼠肺组织病理学变化;检测大鼠肺组织中SIRT1/NF-κB/NLRP3信号通路中的相关蛋白和基因表达水平;检测肝组织中Caspase-1的活性。结果与正常组比较,模型组大鼠炎症细胞数量、炎症因子含量和HE染色显示的病理改变都显著升高,SIRT1表达水平下降,NF-κB、NLRP3、ASC、Caspase-1、IL-1β和IL-18的蛋白水平和mRNA水平显著升高(P<0.05)。与模型组相比,风咳汤高剂量可以显著降低炎症细胞数和炎症因子含量,改善肺组织的病理改变,升高SIRT1的表达水平同时降低NF-κB、NLRP3、ASC和IL-1β的蛋白水平及mRNA水平,其作用与地塞米松相当。此外,风咳汤还可以降低Caspase-1的活性。结论风咳汤可以通过SIRT1/NF-κB/NLRP3信号通路有效改善CVA大鼠气道炎症,改善肺功能。Objective To determine the effect and mechanism of Fengke decoction on trachea inflammation and lung function in rats with cough variant asthma(CVA).Methods The rat model of asthma was sensitized by 1 mL hypodermic injection of ovum protein(OVA)and aluminum hydroxide mixture,and then stimulated by atomized OVA.The rat model was treated with Fengke decoction at low dose,high dose and dexamethasone respectively and the corresponding volume of normal saline was administered by gavage in both the normal control group and the model group.The inflammatory cells in the bronchoalveolar lavage fluid(BALF)were counted by Diff-Quick method.IL-1β,IL-18,IL-17 and IL-22 cytokines in the BALF supernatant were detected by ELISA method.The changes in the lung histopathology were observed by HE staining.Western blot and q-PCR were used to detect the expression levels of SIRT1/NF-κB/NLRP3 signaling pathway in the rat lung tissues.Caspase-1 activity assay kit was used to detect Caspase-1 activity in the liver tissue.Results Compared with the normal group,the number of inflammatory cells,the content of inflammatory factors and the pathological changes shown by HE staining in the model group were obviously increased,and the protein and mRNA levels of NF-κB,NLRP3,ASC,Caspase-1,IL-1βand IL-18 were also much increased(P<0.05),while the expression level of SIRT1 was decreased.Compared with the model group,high dose Fengke decoction significantly reduced the number of inflammatory cells and the content of inflammatory factors,improved the pathological changes in the lung tissue,increased the expression level of SIRT1,and reduced the protein and mRNA levels of NF-κB,NLRP3,ASC,IL-1βand IL-18.The effect was comparable to that of dexamethasone.In addition,Fengke decoction reduced the activity of Caspase-1.Conclusion Fengke decoction can effectively alleviate trachea inflammation and improve the lung function in CVA rats via SIRT1/NF-κB/NLRP3 signaling pathway.

关 键 词：风咳汤 咳嗽变异性哮喘 炎症 SIRT1/NF-κB/NLRP3信号通路 

分 类 号：R285[医药卫生—中药学]