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

doi:10.12122/j.issn.1673-4254.2025.09.03

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (9): 1830-1839.doi: 10.12122/j.issn.1673-4254.2025.09.03

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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

杨勤军¹(), 朱虹宇¹, 高远¹, 杨程², 刘桐¹, 张璐¹, 童佳兵¹^,²^,³, 李泽庚²^,³^,⁴()

^1.安徽中医药大学中医学院，安徽合肥 230038
^2.安徽中医药大学第一附属医院，安徽合肥 230031
^3.中医药防治肺系重大疾病应用转化安徽省重点实验室，安徽合肥 230031
^4.新安医学教育部重点实验室，安徽合肥 230038

收稿日期:2025-04-08 出版日期:2025-09-20 发布日期:2025-09-28
通讯作者: 李泽庚 E-mail:yangqjahtcm@163.com;li6609@126.com
作者简介:杨勤军，副教授，硕士生导师，E-mail: yangqjahtcm@163.com
基金资助:
国家自然科学基金联合重点项目(U20A20398);国家自然科学基金(82374399);2024年度高等学校科研计划项目(2024AH051047);安徽省中医药传承创新科研项目(2024CCCX077)

Sangma Zhike Formula alleviates airway inflammation and hyperresponsiveness in rats with postinfectious cough by inhibiting the TRPV1-SP/CGRP and pyroptosis pathways

Qinjun YANG¹(), Hongyu ZHU¹, Yuan GAO¹, Cheng YANG², Tong LIU¹, Lu ZHANG¹, Jiabing TONG¹^,²^,³, Zegeng LI²^,³^,⁴()

^1.School of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230038, China
^2.First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
^3.Anhui Provincial Key Laboratory for the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei 230031, China
^4.Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230038, China

Received:2025-04-08 Online:2025-09-20 Published:2025-09-28
Contact: Zegeng LI E-mail:yangqjahtcm@163.com;li6609@126.com
Supported by:
National Natural Science Foundation of China(82374399)

摘要/Abstract

摘要：

目的探讨桑麻止咳方（SMZKF）对感染后咳嗽（PIC）大鼠咳嗽敏感性和气道炎症的改善作用及其机制。方法 SD雄性大鼠随机分为对照组，模型组，SMZKF低、中、高剂量组，复方甲氧那明组（ASM），8只/组。除对照组外，其余大鼠采用烟熏+鼻滴脂多糖+辣椒素雾化构PIC大鼠模型，第19天开始灌胃SMZKF和复方甲氧那明，连续10 d。分析各组大鼠行为学状态、咳嗽敏感性、肺组织病理、肺泡灌洗液（BALF）炎性细胞计数和炎性因子/介质、肺组织氧化应激以及咳嗽敏感性和细胞焦亡相关蛋白的表达。结果与对照组比较，模型组大鼠精神欠佳，呼吸加快，出现明显咳嗽、打喷嚏、抓脸等表现；咳嗽潜伏期明显缩短，5 min咳嗽次数增加；肺泡结构消失，肺泡隔增宽，支气管及支气管周围有大量炎性细胞浸润，支气管周围和肺泡炎症评分明显升高；BALF中炎性细胞计数和炎性因子/介质IL-1β、TNF-α、IL-6、COX-2、PGE-2、TXA-2均升高；肺组织ROS、MDA、MPO升高；肺组织咳嗽高敏感性相关蛋白TRPV1、SP、CGRP、NK1R和细胞焦亡相关蛋白P-NF-κB、NLRP3、ACS、cleaved-caspase-1、cleaved-IL-1β和GSDMD-N表达升高（P<0.05）。与模型组比较，SMZKF能改善各项指标的病理改变（P<0.05），且SMZKF高剂量与复方甲氧那明干预效果的差异无统计学意义（P>0.05）。结论 SMZKF能有效改善PIC模型大鼠咳嗽敏感性和气道炎症，其作用机制与抑制TRPV1介导的SP/NK1R与CGRP释放和细胞焦亡途径密切相关。

关键词: 感染后咳嗽, 桑麻止咳方, 咳嗽敏感性, 气道炎症, 机制

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.

Key words: postinfectious cough, Sangma Zhike Formula, cough sensitivity, airway inflammation, mechanism

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.

Qinjun YANG, Hongyu ZHU, Yuan GAO, Cheng YANG, Tong LIU, Lu ZHANG, Jiabing TONG, Zegeng LI. Sangma Zhike Formula alleviates airway inflammation and hyperresponsiveness in rats with postinfectious cough by inhibiting the TRPV1-SP/CGRP and pyroptosis pathways[J]. Journal of Southern Medical University, 2025, 45(9): 1830-1839.

图/表 7

图1 PIC动物模型构建与给药示意图

Fig.1 Schematic diagram of postinfectious cough (PIC) modeling in rats and drug administration.

图2 各组大鼠咳嗽潜伏期和5 min咳嗽次数比较

Fig.2 Cough latency (A) and number of coughs within 5 min (B) in each group. *P<0.05 vs CON group, #P<0.05 vs PIC group.

图3 各组大鼠肺组织病理及支气管和肺泡炎症评分比较

Fig.3 Lung tissue pathology and bronchial and alveolar inflammation scores in each group of rats. A: HE staining of rat lung tissue (Original magnification: ×400). B: Bronchial inflammation scores. C: Alveolar inflammation scores. *P<0.05 vs CON group, #P<0.05 vs PIC group.

图4 各组大鼠BALF炎性细胞计数比较

Fig.4 Inflammatory cell counts in BALF of the rats in each group. A: WBC. B: LYM. C: NEU. D: MON. E: EOS. *P<0.05 vs CON group, #P<0.05 vs PIC group.

图5 各组大鼠BALF炎症因子和炎症介质

Fig.5 Levels of inflammatory factors and mediators in the BALF of the rats in each group. A: IL-1β. B: TNF-α. C: IL-6. D: PGE-2. E: COX-2. F: TXA-2. *P<0.05 vs CON group, #P<0.05 vs PIC group.

图6 各组大鼠肺组织ROS和MDA比较

Fig.6 Levels of ROS and MDA in the lung tissues of the rats in each group. A: Flow cytometry for detecting ROS in the lung tissue. B: ROS. C: MDA. D: MPO. *P<0.05 vs CON group, #P<0.05 vs PIC group.

图7 各组大鼠肺组织气道敏感性相关蛋白的比较

Fig.7 Expressions of airway sensitivity-related proteins in the lung tissues of the rats in each group. A: Western blotting for detecting expressions of TRPV1, SP, CGRP and NK1R in the lung tissue. B: TRPV1. C: SP. D: CGRP. E: NK1R. *P<0.05 vs CON group, #P<0.05 vs PIC group.

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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

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