Protective Effect Of MLIF On Traumatic Brain Injury

Objective:Traumatic brain injury(TBI)is the most common diseases in the trauma.Statistics show that the incidence of traumatic brain injury is the highest among all kinds of traumatic injuries,and its morbidity and mortality are high,seriously affecting people's health and quality of life.With the development of economic and transportation,the incidence of traumatic brain injury is also rising.It is reported that traumatic brain injury can induce brain edema,inflammation and oxidative stress resulting in mortality.Currently,there is a lack of effective drugs to treat traumatic brain injury in the clinic.Therefore,it is urgent to find an effective drug and clarify its mechanism of action.Monocyte locomotion inhibitory factor(MLIF)is a peptide compound secreted by Entamoeba histolytica,which has anti-inflammatory and anti-oxidant effects.The aim of this study is explore the protective effice of MLIF on Traumatic brain injury-induced damage.Methods: 1.Effect of MLIF on TBI in rats:(1)Rats were made model brain injury by Fluid percussion injury(2.0 atm,20ms).(2)Rats groups and administration: sham group,model group,low does group of MLIF ?middle does group of MLIF and high does group of MLIF.The tail vein is administered within 30 min after TBI,once every 24 hours,and rats were administered for 7 days.(3)Rats test index: brain water content;Hematoxylin-eosin staining and Nissl staining;TUNEL staining was used to detect apoptotic cells in rats brain tissuse;Detection of SOD and MDA in rats serum;Immunocytochemistry and Immunofluorescence was use to detect AQP4 expression;The expression of IL-1??IL-6 and TNF-? mRNA were measured by Real-time PCR;The expression of AQP4?Bax and Bcl-2 protein were measured by Weatern Blot.2.Effect of MLIF on TBI in mouse:(1)Mouse were made brain injury model by the falling weight method(weight:20g;high:50cm).(2)Mouse groups and administration: sham group,model group,low does group,medium dose group and high does group.The tail vein is administered within 30 min after TBI.(3)Mouse test index: brain water content;Hematoxylin-eosin staining and Nissl staining.Results: 1.After traumatic brain injury in rats,rats were given MLIF: 1mg / kg and 3mg / kg respectively,the brain water content was lower than the model group,and MLIF(1mg / kg)brain water content was significantly lower than MLIF(3mg / kg).After MLIF(1 mg / kg)was given to rats,brain water content in MLIF group was significantly lower than that in model group(P <0.05).HE staining and Nissl staining showed that the pathological changes of brain tissue in model group were obvious,and MLIF group were improved in brain tissue.Compared the MLIF group with the model group,TUNEL staining showed that MLIF could reduce the apoptosis induced by brain injury.The results of SOD and MDA showed that MLIF could improve oxidative stress,increase SOD activity(P <0.01)and decrease MDA content(P <0.05).2.After traumatic brain injury in mouse,compared with model group,After MLIF(2 mg / kg)was given to mouse,Brain water content decreased significantly(P <0.05).The results of HE staining and Nissl staining showed that the pathological changes of brain tissue in model group were obvious.By contras,brain tissue in MLIF group were improved.3.After traumatic brain injury in rats,compared with model group,the expression of proinflammatory cytokines(P <0.05)was significantly inhibited after administration,and the brain injury was improved.AQP4 immunohistochemistry showed that MLIF reduced AQP4 protein expression(P <0.05).4.Compared with model group,At the protein level,MLIF reduced the expression of AQP4 and Bax and increased the expression of Bcl-2 in brain-induced rats(P<0.05).Conclusion: 1.MLIF(1mg/kg)has a protective effect on traumatic brain injury in rats;MLIF(2mg/kg)has a protective effect on traumatic brain injury in mouse.2.MLIF can inhibit the expression of proinflammatory cytokines(IL-1?,IL-6 and TNF-?),and regulate the expression of AQP4,Bax and Bcl-2 proteins and exert neuroprotective effect after traumatic brain injury.