目的 探究穿心蓮內(nèi)酯調(diào)節(jié)NOD受體蛋白3（NLRP3）/半胱氨酸天冬氨酸蛋白水解酶-1（Caspase-1）信號通路對呼吸道合胞病毒（RSV）感染毛細支氣管炎大鼠炎癥反應(yīng)的影響。方法 34只大鼠采用RSV滴鼻法構(gòu)建毛細支氣管炎大鼠模型，將建模成功的30只大鼠隨機分為對照組、模型組、穿心蓮內(nèi)酯（5、10 mg/kg）組、NLRP3/Caspase-1通路激活劑Nigericin（1.45 mg/kg）組、穿心蓮內(nèi)酯＋Nigericin（10＋1.45 mg/kg）組。分析各組大鼠肺組織含水量和肺指數(shù)；蘇木精–伊紅（HE）檢測肺部病理變化；qRT-PCR檢測肺組織中RSV病毒載量；Western blotting和IHC檢測肺組織蛋白NLRP3、Caspase-1的表達情況；流式細胞術(shù)檢測大鼠外周血Th1/Th2細胞比例；ELISA檢測支氣管肺泡灌洗液（BALF）中腫瘤壞死因子-γ（TNF-γ）、白細胞介素（IL）-6、IL-4的水平。結(jié)果 與模型組相比，穿心蓮內(nèi)酯（5、10 mg/kg）組肺指數(shù)、肺組織含水量及病毒載量減少，肺部損傷得到改善，NLRP3、Caspase-1陽性表達率和蛋白表達、Th2細胞百分含量、TNF-γ、IL-6水平減少，Th1細胞百分含量、BALF中IL-4水平升高（P＜0.05、0.001）；與穿心蓮內(nèi)酯10 mg/kg組組相比，穿心蓮內(nèi)酯＋Nigericin組上述指標表達均相反（P＜0.05、0.01、0.001）。結(jié)論 穿心蓮內(nèi)酯能改善RSV感染毛細支氣管炎大鼠炎癥反應(yīng)，可能是通過抑制NLRP3/Caspase-1通路實現(xiàn)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

張家口市科學(xué)技術(shù)局科技項目（2322087D）