长链酰基辅酶A合成酶4在脓毒症炎症反应中的作用OA

Objective To investigate the role of Acyl-CoA synthetase long chain family member 4(ACSL4)in sepsis and to explore its potential as a therapeutic target for clinical intervention.Methods A sepsis mouse model was established by cecal ligation and puncture(CLP).Mice were randomly assigned to a sham group,a CLP group,and PRGL493 treatment groups receiving an ACSL4-specific inhibitor at doses of 0.125,0.25,or 1 mg/kg.Survival and body weight were monitored for 7 consecutive days.ACSL4 expression in peripheral blood was measured.General condition was assessed using a clinical scoring system.Histopathological changes in the lung,liver,kidney,and spleen were evaluated by hematoxylin and eosin staining.Serum biochemical parameters and inflammatory cytokines were determined by ELISA.Results Compared with the control group,ACSL4 expression in peripheral blood was significantly increased in septic mice in the CLP group.Compared with the CLP group,the 7-day survival rate was significantly improved in the PRGL493-treated groups at 0.125 mg/kg and 0.25 mg/kg(P＜0.05),with the most pronounced protective effect observed at 0.25 mg/kg.PRGL493 treatment reduced the expression of ACSL4 in peripheral blood of septic mice,improved their general condition and clinical scores,alleviated pathological damage to the lung,liver,kidney and spleen In addition,PRGL493 significantly reduced serum levels of creatinine(Crea),blood urea nitrogen(BUN),lactate dehydrogenase(LDH),alanine amin-otransferase(ALT),and aspartate aminotransferase(AST),decreased the pro-inflammatory cytokine TNF-α,and increased the anti-inflammatory cytokine IL-10.Conclusion ACSL4 is highly expressed in the peripheral blood of septic mice.Pharmacological inhibition of ACSL4 with PRGL493 alleviates systemic inflammation and multiple organ injury and improves survival,suggesting that ACSL4 may serve as a promising therapeutic target for sepsis.