The Protective Effects Of Vitamin E On The Cerebral Edema Formation Induced By 1,2-Dichloroethane Poisoning

Objective: 1,2-dichloroethane(1,2-DCE)is one of the commonly organic solvents in the industry.It is highly toxic,fat-soluble,and highly volatile to the air,Workers can quickly inhale high concentrations of 1,2-DCE through the respiratory tract.The brain is the main target organ of 1,2-DCE,and its clinical poisoning performance is mainly toxic encephalopathy,and cerebral edema is its main pathological change.Related literature indicates that the main metabolic pathway of 1,2-DCE in vivo is the production of the more active intermediate metabolites 2-chloroethanol and chloroacetaldehyde by cytochrome P450 2E1(cytochrome P450 2E1,CYP 2E1),and the final transformation as chloroacetic acid is excreted in the urine.Meanwhile,a large amount of reactive oxygen species(ROS)is generated in the metabolic process.A large amount of ROS may cause imbalance of the body's pro-oxidant and antioxidant substances,resulting in oxidative damage.Recent research data indicate that CYP 2E1 is mainly expressed in liver tissue,but CYP 2E1 is also expressed in extrahepatic tissues such as brain tissue.1,2-DCE is fat-soluble,so 1,2-DCE in brain tissue can be metabolized by CYP 2E1 to produce a large amount of ROS,causing oxidative damage to brain tissue,such as deoxyribonucleic acid(DNA),membrane lipid and protein damage.Recent studies have shown that a large amount of ROS in brain tissue affects the expression of tight junction proteins,destroys tight junctions,increases the permeability of the blood-brain barrier,and causes brain edema.Therefore,in this experiment,before the 1,2-DCE exposure,the effect of vitamin E on 1,2-DCE-induced toxic cerebral edema was studied by in vivo experiment to give fat-soluble vitamin E(vita E).Provide experimental and theoretical basis for 1,2-DCE control.Methods: In this study,female SPF mice were adaptively reared and randomly divided into 6 groups,which were solvent control group,VitE control group,1,2-DCE purely exposure group and low dose,medium dose and high dose VitE.group.The mice in solvent control group and the purely exposed group were intragastrically administered with 0.2 ml of corn oil per day;the VitE control group and the low,medium and high dose intervention group mice were given 200,50,100 and 200 mg/kg of VitE per day.Dissolve VitE in corn oil.After 4 days of continuous gavage,mice in the simple exposure group and each intervention group were exposed to static inhalation for 3.5 h after daily gavage,and continued to be exposed for 3 days and the concentration of 1,2-DCE in the poisoning cabinet was 1.2 mg/L.Brain tissue was used to detect brain water content,malondialdehyde(MDA)content and glutathione(GSH)content,superoxide dismutase(SOD)activity and catalase Assay kit(CAT)activity,protein and mRNA expression levels of CYP 2E1,Nrf2 and HO-1,Occludin and Claudin-5,and pathological sections of brain tissue were observed by HE staining.Statistical analysis was performed using SPSS 20.0 software.The test level was P < 0.05.Results: Contrast to solvent control group,the brain tissue of the mice in the simple exposure group showed obvious pathological changes of brain edema.In addition,brain water content,MDA content in brain tissue,protein and mRNA expression levels of CYP2E1,Nrf2 and HO-1 were increased obviously in mice exposed to the virus alone,while GSH content,SOD and CAT activities,Occludin protein and mRNA,and Claudin-5 in brain tissue of the mice were significantly increased.Protein expression levels were significantly reduced(P < 0.05).Compared with the simple exposure group,the brain water content,brain tissue MDA content,protein and mRNA expression levels of CYP2E1,Nrf2 and HO-1 were decreased obviously in each intervention group,while GSH content,Occludin protein and mRNA levels were significantly increased,and moderate and high dose intervention The activity of SOD and CAT and the expression level of Claudin-5 protein in the brain tissue of the group were significantly increased.Conclusion: 1.1,2-DCE exposure can cause brain edema in mice.2.1,2-DCE exposure can significantly induce the expression of CYP2E1 in mouse brain tissue,which in turn can cause oxidative damage,induce the expression of Nrf2 and HO-1,inhibit the expression of Occludin and Claudin-5,destroy tight junction and cause brain edema in mouse brain tissue.3.VitE intervention can reduce oxidative damage caused by 1,2-DCE,restrain CYP2E1 expression,make the expression of Nrf2 and HO-1 reduce in brain tissue and alleviate the effect on tight junction protein.