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

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Abstract: ObjectiveTo investigate the therapeutic mechansm of Sangma Zhike Formula (SMZKF) for relieving cough sensitivityandairwayinflammationinrats withpostinfectiouscough (PIC).MethodsMaleSDratmodelswereestablishedby cigaretesmokeexposure withintranasalLPSinstilationandcapsaicinaerosolinhalation.Fromday19followingthestartof PIC modeling,theratsreceiveddailytreatment withsaline (model group),low-,medium-,andhigh-doseSMZKF,and compound methoxyphenamine (ASM)via gavagefor10consecutivedays (n=8).Theasessments included behavioralchanges, coughensitivity(atencyndfrequency)ungsopathologyinflmmatorycelountsandcyokine/mediatorlelste bronchoalveolarlavagefluid(BALF)oxidativestressmarkersinthelungtisse,andexpressionsofproteinsrelatedwith coughhypersensitivityandpyroptosis.ResultsTheratmodelsof PICexhibitedreducedmentalalertness,accelerated respiration,and pronouncedsymptomssuchasouging,snezing,andfacialscratching withsignificantlyshortenedcough latencyandincreased5-mincoughfrequency.Histopathologicalanalysisrevealedcollpsedalveolarstructures,thickened alveolarseptaandextensiveinflammatorycellinfiltrationinthebronchiandpebroncialgions,ccompanedbylevated bronchialand alveolar inflammationscoresof theratmodels.Inthe BALF,inflammatorycellcountsandthelevelsof L-1β, TNF- α, IL-6, COX-2, PGE-2,and TXA-2 were allmarkedly elevated,and the pulmonaryoxidative stress markers (ROSand MDA)and myeloperoxidase (MPO) activity were also significantly increased.The pulmonary expressions of cough hypersensitivity-relaed proteis (V1,SP,GRPnd)ad potois-ssoied mkers (-F-,,,cleavedcaspase-1,cleavedIL-1β,andGsDMD-N)were significantlyupregulated in the model group. SMZKF interventionssignificantlyamelioratedthesepathological changes in the rat models,and high-dose SMZKF produced a similar therapeutic efficacy to that ofASM. Conclusion SMZKF alleviates cough sensitivity and airwayinflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/ caspase-1/GSDMD pyroptosis pathway.
Keywords:postinfectiouscough;Sangma ZhikeFormula; coughsensitivity;airwayinflammation;mechanism
感染后咳嗽(PIC)是上呼吸道感染后,感染本身急性期症状消失,胸部X线检查无异常,咳嗽仍然迁延不愈的一种常见呼吸系统疾病;临床主要表现为持续3~8周的刺激性干咳和咽部不适,或伴有少量白色黏液痰,通常由病毒、细菌、支原体等因素诱发1。(剩余16536字)