南方医科大学学报2025，Vol.45Issue(9)：1830-1839,10.DOI:10.12122/j.issn.1673-4254.2025.09.03
桑麻止咳方改善感染后咳嗽大鼠气道炎症和敏感性:基于TRPV1-SP/CGRP和细胞焦亡途径
Sangma Zhike Formula alleviates airway inflammation and hyperresponsiveness in rats with postinfectious cough by inhibiting the TRPV1-SP/CGRP and pyroptosis pathways
摘要
Abstract
Objective To investigate the therapeutic mechanism of Sangma Zhike Formula(SMZKF)for relieving cough sensitivity and airway inflammation in rats with postinfectious cough(PIC).Methods Male SD rat models were established by cigarette smoke exposure with intranasal LPS instillation and capsaicin aerosol inhalation.From day 19 following the start of PIC modeling,the rats received daily treatment with saline(model group),low-,medium-,and high-dose SMZKF,and compound methoxyphenamine(ASM)via gavage for 10 consecutive days(n=8).The assessments included behavioral changes,cough sensitivity(latency and frequency),lung histopathology,inflammatory cell counts and cytokine/mediator levels in the bronchoalveolar lavage fluid(BALF),oxidative stress markers in the lung tissue,and expressions of proteins related with cough hypersensitivity and pyroptosis.Results The rat models of PIC exhibited reduced mental alertness,accelerated respiration,and pronounced symptoms such as coughing,sneezing,and facial scratching with significantly shortened cough latency and increased 5-min cough frequency.Histopathological analysis revealed collapsed alveolar structures,thickened alveolar septa,and extensive inflammatory cell infiltration in the bronchi and peribronchial regions,accompanied by elevated bronchial and alveolar inflammation scores of the rat models.In the BALF,inflammatory cell counts and the levels of IL-1β,TNF-α,IL-6,COX-2,PGE-2,and TXA-2 were all markedly elevated,and the pulmonary oxidative stress markers(ROS and MDA)and myeloperoxidase(MPO)activity were also significantly increased.The pulmonary expressions of cough hypersensitivity-related proteins(TRPV1,SP,CGRP,and NK1R)and pyroptosis-associated markers(P-NF-κB,NLRP3,ACS,cleaved caspase-1,cleaved IL-1β,and GSDMD-N)were significantly upregulated in the model group.SMZKF interventions significantly ameliorated these pathological changes in the rat models,and high-dose SMZKF produced a similar therapeutic efficacy to that of ASM.Conclusion SMZKF alleviates cough sensitivity and airway inflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/caspase-1/GSDMD pyroptosis pathway.关键词
感染后咳嗽/桑麻止咳方/咳嗽敏感性/气道炎症/机制Key words
postinfectious cough/Sangma Zhike Formula/cough sensitivity/airway inflammation/mechanism引用本文复制引用
杨勤军,朱虹宇,高远,杨程,刘桐,张璐,童佳兵,李泽庚..桑麻止咳方改善感染后咳嗽大鼠气道炎症和敏感性:基于TRPV1-SP/CGRP和细胞焦亡途径[J].南方医科大学学报,2025,45(9):1830-1839,10.基金项目
国家自然科学基金联合重点项目(U20A20398) （U20A20398）
国家自然科学基金(82374399) （82374399）
2024年度高等学校科研计划项目(2024AH051047) （2024AH051047）
安徽省中医药传承创新科研项目(2024CCCX077)Supported by National Natural Science Foundation of China(82374399). （2024CCCX077）
