Expression Levels Of CYP2E1 In Different Brain Regions And The Effects On 1,2-DCE Induced Cerebral Edema Formation

Objective: 1,2-Dichloroethane(1,2-Dichloroethane,1,2-DCE)is a commonly used organic solvent in the industry.It is a halogenated hydrocarbon compound.It is a colorless and odorless oily liquid at room temperature.Highly toxic chemicals for the production of adhesives and chlorinated hydrocarbons.1,2-DCE is highly volatile and forms a higher concentration in the air,which is absorbed by the respiratory tract,digestive tract,and skin.Because 1,2-DCE is a non-polar fat-soluble small molecule,1,2-DCE entering the body can easily enter the brain tissue through the blood brain barrier(BBB).Therefore,brain tissue is the main target organ for 1,2-DCE in humans.Subacute 1,2-DCE poisoning can cause toxic encephalopathy,and its main pathological change is cerebral edema.Research data show that cytochrome P4502E1(cytochrome P4502E1,CYP2E1)is one of the key enzymes for 1,2-DCE metabolism in the body.Metabolism of 1,2-DCE through CYP2E1 can produce chloroacetaldehyde,which is a more active intermediate.CYP2E1 is prone to uncoupling electron transfer during the metabolic reaction of the catalytic substrate,which in turn generates a large number of reactive oxygen species(ROS).Studies have shown that ROS can disrupt the tight junctions of BBB,thereby increasing the permeability of BBB and inducing brain edema.Therefore,the expression level of CYP2E1 in brain tissue can affect the metabolism of1,2-DCE in brain tissue,and then affect the production of its active intermediate metabolites chloroacetaldehyde and ROS and brain tissue damage.Studies have confirmed that CYP2E1 is expressed at different levels in different brain regions.This study intends to explore the relationship between CYP2E1 expression and brain tissue damage in different brain regions of mice during 1,2-DCE exposure through animal experiments,and to reveal the role of CYP2E1 in the formation of toxic cerebral edema in 1,2-DCE.Methods: Forty healthy female Kunming mice were selected and randomly divided into blank control group,1 d,2 d and 3 d groups.The inhalation was performed by static inhalation.The mice were placed in a 100 L exposure cabinet at a concentration of 1.2mg / L,and the exposure was 3.5 hours a day,respectively for 1 d,2 d,and 3 d.Thegroup was not infected,and other treatment methods were the same as those of the exposed group.The mice were sacrificed the next day after the exposure,and the cerebellum and frontal cortex were quickly taken.The water content in different brain regions and the protein and mRNA expression levels of CYP2E1,Occludin,claudin5 and MMP-9 were measured.Tissues were stained with HE staining.Pathological observations were performed using kits to detect malondialdehyde(MDA)and reduced glutathione(GSH)content and catalase(CAT)activity in different brain regions.Results: 1.Compared with the control group,the content of CYP2E1 protein and the relative expression level of mRNA in cerebellar tissue of mice exposed to 3 d were significantly increased(p <0.05),and the expression of CYP2E1 protein in cerebellum of mice exposed to 3 d The levels were also significantly higher than those on the 1 and 2 d exposure groups.There was no significant difference in the expression levels of CYP2E1 protein and mRNA in the frontal cortex of mice in each group.The midbrain water content in cerebellar tissue of mice in each exposure group was higher than that in the control group,and there was no significant difference in midbrain water content in frontal cortex of mice in each group.In addition,compared with the control group,histopathological observations showed that brain edema such as cell swelling and light cytoplasmic staining appeared in the brain tissues on the 2nd and 3d groups,and the frontal cortex of mice in each group was not changed.See obvious pathological changes in cerebral edema.2.Compared with the control group,the MDA content in the cerebellar tissue of the mice exposed to the 2nd and 3d groups was significantly increased(p <0.05),and there was no significant change in the MDA content of the frontal cortex of the mice in each group;The CAT activity and GSH content in the cerebellar tissue of the mice in the exposure group were significantly lower than those in the control group(p <0.05),and there was no significant difference in the CAT activity and GSH content in the frontal cortex of the mice in each group.3.The expression levels of MMP-9 protein and mRNA in cerebellar tissue of mice exposed to 2 d and 3 d groups were significantly higher than those in the control group(p <0.05).The content of Occludin and Claudin-5 protein in the cerebellar tissue of mice in each exposure group was significantly lower than that in the control group(p <0.05).There was no significant difference in the content of Occludin and Claudin-5 protein in the frontal cortex of micein each group.Conclusions: 1.1,2-DCE exposure can induce the expression of CYP2E1 in cerebellar tissue of mice,but has no significant effect on the expression of CYP2E1 in the frontal cortex.2.1,2-DCE exposure can cause oxidative damage and cerebral edema in the cerebellar tissue of mice,while its frontal cortex shows no obvious damage.3.CYP2E1-mediated 1,2-DCE metabolism in the brain plays an important role in brain injury caused by 1,2-DCE exposure.