目的 探究穿心莲内酯调节NOD受体蛋白3（NLRP3）/半胱氨酸天冬氨酸蛋白水解酶-1（Caspase-1）信号通路对呼吸道合胞病毒（RSV）感染毛细支气管炎大鼠炎症反应的影响。方法 34只大鼠采用RSV滴鼻法构建毛细支气管炎大鼠模型，将建模成功的30只大鼠随机分为对照组、模型组、穿心莲内酯（5、10 mg/kg）组、NLRP3/Caspase-1通路激活剂Nigericin（1.45 mg/kg）组、穿心莲内酯＋Nigericin（10＋1.45 mg/kg）组。分析各组大鼠肺组织含水量和肺指数；苏木精–伊红（HE）检测肺部病理变化；qRT-PCR检测肺组织中RSV病毒载量；Western blotting和IHC检测肺组织蛋白NLRP3、Caspase-1的表达情况；流式细胞术检测大鼠外周血Th1/Th2细胞比例；ELISA检测支气管肺泡灌洗液（BALF）中肿瘤坏死因子-γ（TNF-γ）、白细胞介素（IL）-6、IL-4的水平。结果 与模型组相比，穿心莲内酯（5、10 mg/kg）组肺指数、肺组织含水量及病毒载量减少，肺部损伤得到改善，NLRP3、Caspase-1阳性表达率和蛋白表达、Th2细胞百分含量、TNF-γ、IL-6水平减少，Th1细胞百分含量、BALF中IL-4水平升高（P＜0.05、0.001）；与穿心莲内酯10 mg/kg组组相比，穿心莲内酯＋Nigericin组上述指标表达均相反（P＜0.05、0.01、0.001）。结论 穿心莲内酯能改善RSV感染毛细支气管炎大鼠炎症反应，可能是通过抑制NLRP3/Caspase-1通路实现的。

Objective To investigate the effect of andrographolide on inflammatory response in bronchiolitis rats with respiratory syncytial virus (RSV) infection with bronchiolitis by modulating the NLRP3/Caspase-1 signaling pathway. Methods Thirty-four rats were selected and the rat model of bronchiolitis was constructed by RSV nasal drop. The 30 rats with successful modeling were randomly divided into control group, model group, andrographolide (5, 10 mg/kg) group, Nigericin group, and andrographolide + Nigericin group (10 + 1.45 mg/kg). The water content and lung index of lung tissue in each group were analyzed. HE was used to detect pathological changes in the lungs. RSV viral load in lung tissue was detected by qRT-PCR. Western blotting and IHC were used to detect the expressions of NLRP3 and Caspase-1 in lung tissue. Flow cytometry was used to detect the ratio of Th1/Th2 cells in rat peripheral blood. The levels of TNF-γ, IL-6, and IL-4 in bronchoalveolar lavage fluid (BALF) were detected by ELISA. Results Compared with the model group, the lung index, lung tissue water content, and viral load of andrographolide (5, 10 mg/kg) group were reduced, and the lung injury was improved, the positive expression rate, the protein expression rates of NLRP3 and Caspase-1, the percentage content of Th2 cells, levels of TNF-γ, and IL-6 decreased, the percentage of Th1 cells, and the level of IL-4 in BALF increased (P < 0.05, 0.001). Compared with the andrographolide 10 mg/kg group, the above indexes in andrographolide + Nigericin group were opposite (P < 0.05, 0.01, 0.001). Conclusion Andrographolide can improve the inflammatory response in RSV infected bronchiolitis rats, possibly by inhibiting the NLRP3/Caspase-1 pathway.

R286.4

张家口市科学技术局科技项目（2322087D）