血必净注射液对PINK1/Parkin介导的急性肺损伤大鼠线粒体自噬和细胞焦亡的影响OA

Objective To investigate the mechanism of Xuebijing Injection(XBJ)in inhibiting pyroptosis against acute lung injury(ALI)through the PTEN-induced putative kinase 1(PINK1)/Parkin E3 ubiquitin protein ligase(Parkin)mitophagy pathway.Methods Male SD rats were randomly divided into normal group,model group,low-dose XBJ group,high-dose XBJ group,and dexamethasone sodium phosphate injection group,with 10 rats in each group.An ALI rat model was established by intraperitoneal injection of lipopolysaccharide.After successful model replication,drugs were administered intraperitoneally once daily for 3 consecutive days.The degree of pulmonary edema was assessed by measuring the wet/dry weight ratio of lung tissue.Hematoxylin-eosin(HE)staining was used to observe inflammatory infiltration and damage in lung tissue,and pathological scores were assigned.Serum levels of inflammatory factors interleukin(IL)-1β,IL-17,IL-18,and IL-8 were detected by ELISA.RT-qPCR and Western Blot were performed to measure the mRNA and protein expression levels of PINK1/Parkin pathway components,mitophagy-related proteins BCL-2/adaptor molecule 3 like(BNIP3L)and microtubule-associated protein 1 light chain 3(LC3),and pyroptosis-related proteins NOD-like receptor family pyrin domain containing 3(NLRP3),cysteinyl aspartate-specific protease 1(Caspase-1),and gasdermin D(GSDMD)in lung tissue.Results Compared with the normal group,the model group showed a significant increase in the lung wet/dry weight ratio(P＜0.001),damaged lung tissue structure with extensive inflammatory cell infiltration,elevated lung tissue pathological scores(P＜0.001),increased serum levels of inflammatory factors IL-1β,IL-17,IL-18,and IL-8(P＜0.001),and significantly elevated mRNA and protein levels of PINK1,Parkin,BNIP3L,LC3,NLRP3,and GSDMD,as well as mRNA levels of Caspase-1 and protein levels of Cle Caspase-1 in lung tissue(P＜0.01,P＜0.001).Compared with the model group,the XBJ groups exhibited a significant reduction in the lung wet/dry weight ratio(P＜0.01,P＜0.001),marked improvement in lung tissue damage and inflammatory infiltration,decreased lung tissue pathological scores(P＜0.01,P＜0.001),reduced levels of inflammatory factors IL-1β,IL-17,IL-18,and IL-8(P＜0.05,P＜0.01,P＜0.001),and significantly decreased mRNA and protein levels of PINK1,Parkin,BNIP3L,LC3,NLRP3,and GSDMD,as well as mRNA levels of Caspase-1 and protein levels of Cle Caspase-1 in lung tissue(P＜0.05,P＜0.01,P＜0.001).Conclusion Xuebijing Injection ameliorates lung tissue damage and inflammatory response in rats with ALI,and its mechanism may be related to the downregulation of the PINK1/Parkin mitophagy pathway and inhibition of pyroptosis.