时珍国医国药2025，Vol.36Issue(8)：1401-1408,8.DOI:10.70976/j.1008-0805.SZGYGY-2025-0801
定喘颗粒抑制NLRP3/Caspase-1/GSDMD信号通路介导RSV肺炎幼鼠肺泡上皮细胞焦亡的机制研究
Study on mechanism of Dingchuan Granule(定喘颗粒)in inhibiting NLRP3/Caspase-1/GS-DMD signaling pathway-mediated pyroptosis of alveolar epithelial cells in young rats with RSV pneumonia
摘要
Abstract
Objective To investigate the effect and mechanism of Dingchuan Granule(定喘颗粒,DCG)on respiratory syncytial virus(RSV)-induced pneumonia and pyroptosis in young rats through the NOD-like receptor protein 3(NLRP3)/Caspase-1/Gasdermin D(GSDMD)signaling pathway.Methods Thirty SPF grade SD rats aged 3 to 4 weeks were randomly divided into the control group,model group,ribavirin group,and low/high-dose DCG groups.Except for the control group,all groups were molded by RSV nasal drip and sacrificed after continuous administration for 7 days.Lung tissues were weighed to calculate the lung wet/dry weight ratio(W/D).The total lung injury score was observed and calculated by hematoxylin-eosin(HE)staining.The mRNA expressions of NLPR3,Caspase-1 and GSDMD in the lung tissues were detected by RT-qPCR.The contents of IL-1β and IL-18 in bronchoalveolar lavage fluid(BALF)were detected by ELISA.The protein expression of ZO-1,occludin,NLRP3,Caspase-1 and GSDMD in the lung tis-sues was detected by Western blot(WB).Results Compared with the control group,the model group showed significantly increased W/D ratio and lung injury scores(P<0.01),decreased ZO-1 and occludin protein expressions(P<0.01),upregulated mRNA and pro-tein expressions of NLRP3,Caspase-1,and GSDMD,and elevated IL-18 and IL-1β expressions in BALF(P<0.01).Compared with the model group,all treatment groups exhibited reduced W/D ratios and lung injury scores,increased ZO-1 and occludin expres-sion,and downregulated expressions of NLRP3,Caspase-1,GSDMD protein,mRNA and IL-18/IL-1β of BALF(P<0.05,P<0.01).Conclusion The therapeutic mechanism of DCG against RSV-induced pneumonia in young rats is associated with downregulat-ing the NLRP3/Caspase-1/GSDMD pathway,inhibiting of alveolar epithelial pyroptosis,and restoring tight junctions in the alveolar-capillary barrier.关键词
定喘颗粒/呼吸道合胞病毒/肺炎/核苷酸结合寡聚化结构域样受体蛋白3炎症小体/细胞焦亡Key words
Dingchuan Granule(定喘颗粒)/Respiratory syncytial virus/Pneumonia/NOD-like receptor protein 3 inflam-masome/Pyroptosis分类
医药卫生引用本文复制引用
张诗瑶,张秀英,赵航宇,魏晨浩,王咏雪..定喘颗粒抑制NLRP3/Caspase-1/GSDMD信号通路介导RSV肺炎幼鼠肺泡上皮细胞焦亡的机制研究[J].时珍国医国药,2025,36(8):1401-1408,8.基金项目
国家自然科学基金(8197152087) （8197152087）
