【摘要】 目的：探究雷公藤甲素（TPL）通过抑制Caspase-1诱导的细胞焦亡对博来霉素（BLM）所致肺纤维化（PF）小鼠的作用机制。方法：采用BLM诱导PF模型，将60只C57BL/6雄性小鼠随机分为6组：对照组、模型组、TPL低剂量组、TPL中剂量组、TPL高剂量组及吡非尼酮（PFD）组。28 d后测定肺组织中羟脯氨酸（HYP）含量，HE和Masson染色观察肺部炎症和纤维化水平，ELISA检测PF小鼠血清中白介素（IL）-18和IL-1β的含量。采用Western Blot评估PF小鼠肺组织中蛋白表达水平。结果：与模型组比较，PFD组和TPL各剂量组小鼠肺组织结构正常，炎性细胞浸润减少；蓝色胶原纤维组织较少，肺组织纤维化程度得到缓解；HYP含量以及IL-18、IL-1β水平显著下调（P<0.05,P<0.01）；肺组织中Col-1、α-SMA、Caspase-1、GSDMD、NLRP3、p-AMPK/AMPK蛋白表达显著下降（P<0.05,P<0.01）。结论：TPL可以通过抑制Caspase-1相关蛋白水平，调控细胞焦亡途径，有效改善BLM诱导的小鼠肺纤维化。更多还原

【Abstract】 Objective: To investigate the effect mechanism of Triptolide(TPL) on Bleomycin(BLM)-induced pulmonary fibrosis(PF) in mice by inhibiting cell pyrodeath induced by Caspase-1. Methods: Using BLM-induced PF model, 60 male C57 BL/6 mice were randomly divided into six groups: control group, model group, TPL low-dose group, TPL medium-dose group, TPL high-dose group and PFD group. After 28 days, the content of HYP in lung tissue was determined, the levels of pulmonary inflammation and fibrosis were observed by HE and Masson staining, and the contents of interleukin(IL)-18 and IL-1β in serum of mice with PF were detected by ELISA. Western Blot was used to evaluate the protein expression levels in the lung tissues of mice with PF. Results: Compared with the model group, the lung tissue structure of PFD and TPL groups was normal, and inflammatory cell infiltration was reduced, the blue collagen fiber tissue was less, and the degree of PF was relieved, HYP content, IL-18 and IL-1β levels were significantly decreased(P<0.05, P<0.01), the expression of Col-1, α-SMA, Caspase-1, GSDMD, NLRP3 and p-AMPK/AMPK in lung tissue were significantly decreased(P<0.05, P<0.01). Conclusion: TPL can effectively improve BLMinduced PF in mice by inhibiting the level of Caspase-1-related protein and regulating the pyrodeath pathway.更多还原