中药药理与临床2025，Vol.41Issue(11)：16-20,5.
五虎汤调节NLRP3/Caspase-1/GSDMD信号通路对呼吸道合胞病毒诱发哮喘小鼠肺组织细胞焦亡的影响
Effect of Wuhu Decoction on Pulmonary Tissue Cell Pyroptosis in RSV-Induced Asthmatic Mice by Regulating NLRP3/Caspase-1/GSDMD Signaling Pathway
摘要
Abstract
Objective:To investigate the effects of Wuhu Decoction(五虎汤)on pyroptosis in mice with respiratory syncytial virus(RSV)-induced asthma by regulating the NOD-like receptor protein 3(NLRP3)/Caspase-1/gasdermin D(GSDMD)signaling pathway.Methods:Sixty spe-cific-pathogen free(SPF)-grade male BALB/c mice were randomly divided into a normal control group,a model control group,Wuhu Decoc-tion groups of 1.6 g/kg,3.2 g/kg,and 6.4 g/kg,and a dexamethasone group of 1.8 mg/kg.Asthma was induced by inhalation of a mixture of RSV and ovalbumin(OVA).After successful modeling,each group received the corresponding drug intervention for two weeks.Airway re-activity values were measured using a small animal ventilator.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe pathological changes in lung tissue,mucus secretion by goblet cells,and airway collagen deposition,respectively.A transmission electron microscope was employed to observe the ultrastructural changes in lung tissue.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the levels of interleukin(IL)-18,IL-1β,inflammasome NLRP3,and Caspase-1 in lung tissue.Western blot analysis was conducted to measure the protein levels of NLRP3,Caspase-1,and GSDMD in lung tissue of each group.Results:Compared with the normal control group,the model control group showed a significant increase in airway reactivity(P<0.01),severe damage to lung tissue structure,an increase in mucus secretion by goblet cells,extensive deposition of airway collagen,and severe damage to lung tissue ultrastruc-ture.The level of IL-18,IL-1β,NLRP3,and Caspase-1 in lung tissue was significantly increased(P<0.01),and the expression of NLRP3,Caspase-1,and GSDMD proteins was significantly increased(P<0.01).Compared with the model control group,the Wuhu Decoction group and the dexamethasone group showed significantly decreased airway reactivity in mice(P<0.01),alleviated damage to lung tissue structure,reduced mucus secretion by goblet cells,alleviated airway collagen deposition,and reduced damage to lung tissue ultrastructure.The level of IL-18,IL-1β,inflammasome NLRP3,and Caspase-1 in lung tissue was significantly decreased(P<0.01),and the expression of NLRP3,Caspase-1,and GSDMD proteins was downregulated(P<0.05 or P<0.01).Conclusion:Wuhu Decoction can inhibit the occurrence of py-roptosis by downregulating the NLRP3/Caspase-1/GSDMD signaling pathway,thereby reducing airway inflammation and airway remodeling in RSV-induced asthma mice and decreasing airway hyperresponsiveness.关键词
五虎汤/呼吸道合胞病毒/哮喘/细胞焦亡/NOD样受体热蛋白结构域相关蛋白3/人胱天蛋白酶-1/消皮素D通路Key words
Wuhu Decoction/Respiratory syncytial virus/Asthma/Pyroptosis/NOD-like receptor protein 3/Caspase-1/gasdermin D pathway引用本文复制引用
丁伊,邓羿駃,刘靖雷,姚冰,王孟清,胡燕,罗菁..五虎汤调节NLRP3/Caspase-1/GSDMD信号通路对呼吸道合胞病毒诱发哮喘小鼠肺组织细胞焦亡的影响[J].中药药理与临床,2025,41(11):16-20,5.基金项目
国家自然科学基金项目(编号:82174437) （编号:82174437）
湖南省自然科学基金项目(编号:2023JJ60260、2024JJ6361) （编号:2023JJ60260、2024JJ6361）
湖南省中医药管理局项目(编号:A2024027) （编号:A2024027）
长沙民政职业技术学院教授、博士科研项目(编号:2023JB42) （编号:2023JB42）
广东省中医药局中医药科研项目(编号:20241256) （编号:20241256）
南山区卫生健康系统科技重大项目(编号:NSZD2024055) （编号:NSZD2024055）
全国名老中医药专家传承工作室建设项目(编号:国中医药人教函[2022]75号) （编号:国中医药人教函[2022]75号）
深圳市中医重点学科建设资助. （）
