脾脏X线照射对脓毒症相关急性肝损伤的保护作用OA

Objective To investigate the protective effect and underlying mechanisms of early lowdose splenic X-ray irradiation(Irra)against sepsisassociated acute liver injury(SALI).Methods The sepsis model was estab-lished by classic cecal ligation and puncture(CLP)to induce sepsis-associated acute liver injury(SALI).At 6 hours postoperation,the spleen was locally irradiated with Xrays(8 Gy).One hundred and twenty male SD rats were randomly assigned to two major cohorts(n=60)for either survival observation or endpoint analysis.Each cohort was further divided into four subgroups(n=15):Sham,Sham+Irra,CLP,and CLP+Irra.The 7day survival rate and spleen index were recorded.Serum ALT,AST and hepatic cytokines(IL6,IL1 β,TNFα)were measured by ELISA.Levels of Fe2+,GSH,and MDA in liver tissues were determined.Histopathological chan-ges(H&E staining),mitochondrial ultrastructure(TEM),macrophage markers CD68 and CD206(ICH),and reactive oxygen species(ROS)were assessed.Protein expression of GPX4,ACSL4,and SLC7A11 was assessed by Western blotting.Results Compared with the CLP group,CLP+Irra significantly improved the 7 day survival rate and liver function,attenuated histopathological and mitochondrial damage,and reduced hepatic levels of the proinflammatory cytokines IL6,IL1β,and TNFα(P＜0.01).Irradiation also promoted the shift of hepatic macrophages from the M1 to the M2 phenotype(P＜0.01),decreased levels of ROS,Fe2+,and MDA,and re-stored GSH content(P＜0.01).Moreover,irradiation upregulated the expression of SLC7A11 and GPX4 while downregulating ACSL4 compared with the CLP group(P＜0.01).Conclusion Splenic Xray irradiation protects against SALI,potentially through a mechanism involving the inhibition of the ferroptosis pathway.