雷公藤甲素通过抑制Caspase-1诱导的细胞焦亡对小鼠肺纤维化的作用机制OA

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 C57BL/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 BLM-induced PF in mice by inhibiting the level of Caspase-1-related protein and regulating the pyrodeath pathway.