南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (9): 1500-1508.doi: 10.12122/j.issn.1673-4254.2023.09.07

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参芪温肺方减轻慢性阻塞性肺疾病大鼠的肺气虚证：基于调节NLRP3/GSDMD细胞焦亡通路

吴 迪，王小乐，高雅婷，童佳兵，杨勤军，丁焕章，张 璐，李泽庚   

  1. 安徽中医药大学 中医学院，安徽 合肥 230038；江西中医药大学附属医院，江西 南昌 330006；安徽省中医药科学院中医呼吸病防治研究所//安徽省教育厅中医药防治肺系重大疾病重点实验室//安徽中医药大学第一附属医院，安徽 合肥 230031
  • 出版日期:2023-09-20 发布日期:2023-09-28

Shenqi Wenfei Formula alleviates chronic obstructive pulmonary disease in rats with pulmonary qi deficiency syndrome by regulating NLRP3/GSDMD pyroptosis pathway

WU Di, WANG Xiaole, GAO Yating, TONG Jiabing, YANG Qinjun, DING Huanzhang, ZHANG Lu, LI Zegeng   

  1. School of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230038, China; Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China; Institute of Respiratory Disease Prevention and Treatment in Traditional Chinese Medicine, Anhui Academy of Chinese Medicine//Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Lung Diseases, Anhui Provincial Department of Education//First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
  • Online:2023-09-20 Published:2023-09-28

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摘要： 目的 探讨参芪温肺方（SQWF）对香烟烟雾联合脂多糖（LPS）诱导的慢性阻塞性肺疾病（COPD）肺气虚证模型大鼠NLRP3/GSDMD 信号通路的影响。方法 将 SD 大鼠随机分为空白组（10 mL/kg，8 只）、模型组（10 mL/kg，8 只）、SQWF低（2.835 g/kg，8只）、中（5.67 g/kg，8只）、高（11.34 g/kg，8只）剂量组、玉屏风组（1.35 g/kg，8只），建立COPD肺气虚证大鼠模型。观察大鼠体质量、抓力、肺功能、肺组织病理改变、检测外周血中炎性细胞和BALF中炎症因子水平；Q-PCR及免疫组化法检测肺组织NLRP3/GSDMD信号通路相关分子的表达。结果 与空白组相比，模型组大鼠体质量、抓力及肺功能均降低（P<0.01）、肺组织病理损伤较重；外周血中WBC、NEU%、MON%水平升高（P<0.01），LYM%降低（P<0.01），BALF中TNF-α、IL-6、IL-1β、IL-18含量均升高（P<0.01）；肺组织中NLRP3、ASC、GSDMD、IL-1β、mRNA及其蛋白表达水平升高（P<0.01），与模型组相比，SQWF各组及玉屏风组的体质量、抓力、肺功能及肺组织病理明显改善（P<0.05）；WBC、NEU%及MON%水平降低（P<0.01），LYM%升高（P<0.01），TNF-α、IL-6、IL-1β、IL-18含量均降低（P<0.01）；肺组织NLRP3、ASC、GSDMD及IL-1β的mRNA和蛋白阳性表达水平下调（P<0.05），而Caspase-1和IL-18的 mRNA水平下调不显著（P>0.05），且SQWF呈浓度依赖性。结论 参芪温肺方可能通过调节NLRP3/GSDMD通路抑制肺组织细胞焦亡，缓解COPD肺气虚证大鼠炎症反应，减轻肺组织炎性损伤。

关键词: 参芪温肺方, 慢性阻塞性肺疾病, NLRP3/GSDMD, 细胞焦亡

Abstract: Objective To investigate the effects of Shenqi Wenfei (SQWF) Formula on the NLRP3/ GSDMD signaling pathway in pulmonary qi deficiency syndrome rats with chronic obstructive pulmonary diseases (COPD). Methods Rat models of COPD and lung qi deficiency syndrome induced by exposure to cigarette smoke and lipopolysaccharide (LPS) injection were randomized (n=8) for treatment with low-, medium- and high-dose SQWF or Yu Ping Feng (YPF). The changes in body weight, grip strength, lung function, pulmonary pathology, peripheral blood inflammatory cell counts, and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were examined. The expressions of proteins associated with the NLRP3/GSDMD signaling pathway in the lung tissues were determined with RT-qPCR and immunohistochemistry. Results The rat models of COPD and lung qi deficiency syndrome showed significantly reduced body weight, grip strength and lung function (P<0.01) with severe lung pathologies, increased levels of WBC, NEU% and MON% (P<0.01), decreased LYM% (P<0.01), and increased levels of TNF-α, IL-6, IL-1β and IL-18 in the BALF (P<0.01); the mRNA and protein expression levels of NLRP3, ASC, GSDMD and IL-1β all increased significantly in the lung tissue (P<0.01). Treatment with SQWF and YPF obviously increased body weight and improved grip strength, pulmonary function and lung pathology of the COPD rats (P<0.05). The treatments obviously improved the changes in peripheral blood inflammatory cell counts and inflammatory factors in the BALF of the rat models (P<0.01) and lowered the expressions of NLRP3, ASC, GSDMD and IL- 1β in the lung tissues (P<0.05) without significantly affecting the mRNA levels of caspase-1 and IL-18 (P>0.05), and the effects of SQWF were dose-dependent. Conclusion SQWF Formula relieves inflammatory response and injury in the lung tissue of COPD rats with pulmonary qi deficiency syndrome possibly by inhibiting pyroptosis through regulating the NLRP3/GSDMD pathway.

Key words: ShenqiWenfei Formula, chronic obstructive pulmonary disease, NLRP3/GSDMD, pyroptosis