Study On The Protective Mechanism Of ANXA1sp Against Sepsis-associated Encephalopathy

Objective: Sepsis-associated encephalopathy(SAE)has high morbidity and mortality,and lacking effective treatments.The pathogenesis of SAE is still unclear.This experiment intends to establish a rat model of SAE,and explore the protective effects and mechanisms of Annexin A1 Tripeptide(ANXA1sp)on SAE,and provide new ideas for the prevention and treatment of SAE.Methods: Rat models of SAE were established by intraperitoneal injection with lipopolysaccharide(5mg/kg)and randomly divided into 4 groups: Control group(injection of equal volume of LPS saline control group),SAE group,Vehicle group(SAE + normal saline group),ANSP1 group(SAE+ANXA1sp group).The water maze was used to evaluate the learning and memory abilities of rats,and the open field experiment was used to detect their behavioral abilities.Magnetic resonance imaging DTI technology was used to observe the microstructural changes in the hippocampus,and normal rats were added as normal group for comparing with other groups.To observe the changes of mitochondrial membrane potential,ATP and ROS in hippocampus of SAE rats after ANXA1 sp treatment.Western blot was used to detect the expression of PPAR-? and apoptosis-related proteins,and PPAR-? specific inhibitor T0070907 was added as a comparison to observe the action pathway of ANXA1.Results: 1.Compared with the Control group,the levels of IL-6 and TNF-? in the SAE group were significantly increased(p<0.05);compared with the SAE group,the levels of IL-6 and TNF-? in the ANXA1 sp group were significantly reduced(p<0.05);2.The escape latency of the SAE group on the 4th day was significantly longer than that of the Control group(p<0.05),and the escape latency of the ANXA1 sp group was significantly shorter than SAE group(p<0.05);compared with the Control group,the times of crossing the target of SAE group rats significantly Decreased(p<0.05),he times of crossing the target in the ANXA1 sp group was higher than that in the SAE group(p<0.05).3.Compared with the control group,the activity time of the central area of the SAE group was significantly reduced(p<0.05),and the activity time of the central area of the ANXA1 sp group was increased(p<0.05).4.The DTI scan of the hippocampus showed that the FA value of the SAE group decreased significantly(p<0.05)and the MD value increased significantly(p<0.05)compared with the Control group.Compared with the SAE group,the FA value of the ANXA1 sp group increased significantly,and the MD value decreased significantly(p<0.05).5.Compared with the Control group,the ROS production in the SAE group was significantly increased(p<0.05),the ROS production in the ANXA1 sp group was significantly reduced(p<0.05).6.The red/green fluorescence ratio of the SAE group was significantly lower than that in the Control group,and the red/green fluorescence ratio of the ANXA1 sp group was significantly higher than that in the SAE group(p<0.05).7.Compared with the Control group,the ATP production of the SAE group was significantly reduced(p<0.05),and the ATP production of the ANXA1 sp group was significantly higher than that of the SAE group(p<0.05).8.Compared with the other four groups,the expression of PPAR-? protein was significantly increased in the ANXA1 sp group(p<0.05);compared with the Control group,the expressions of apoptosis-related proteins NF-?B,bax,and caspase-3 in the SAE group and Vehicle group Significantly increased(p<0.05),bcl-2 expression was significantly reduced(p<0.05),NF-?B,bax,caspase-3 expression was significantly reduced in ANXA1 sp group compared with SAE group,bcl-2 expression was significantly increased(p<0.05).Conclusion: 1.Hippocampal microstructural damage is one of the reasons leading to changes in behavior and cognitive function during SAE.2.ANXA1 sp alleviates tissue damage during SAE through the PPAR-? pathway and exerts brain protection.