摘 要: 目的 探讨维生素E(vitamin E,Vit E)对1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)中毒性脑水肿的保护作用。方法 将雌性昆明种小鼠随机分为空白对照组、Vit E对照组、1,2-DCE单纯染毒组及Vit E低、中和高剂量干预组。连续给予药物灌胃4 d后,采取静式吸入方式染毒3.5 h/d,持续3 d。 结果 与空白对照组相比,单纯染毒组小鼠脑组织呈现明显脑水肿病理改变,脑含水量、脑组织中丙二醛(malondialdehyde,MDA)含量及细胞色素P450 2E1(cytochrome P450 2E1,CYP2E1)蛋白和mRNA表达水平显著升高,脑组织中还原型谷胱甘肽(glutathione,GSH)含量、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase assay kit,CAT)活性、Occludin蛋白和mRNA及Claudin 5蛋白表达水平显著降低。与单纯染毒组相比,各干预组小鼠的脑含水量、脑组织MDA含量、CYP2E1蛋白和mRNA表达水平显著降低,GSH含量、Occludin蛋白及mRNA水平显著升高;中和高剂量干预组的小鼠脑组织中SOD和CAT活性及Claudin 5蛋白表达水平亦显著升高(P<0.05)。结论 单纯1,2-DCE染毒可引起小鼠脑水肿,诱导脑组织中CYP2E1的表达,诱发脑组织氧化损伤,破坏紧密连接蛋白,并抑制Occludin和Claudin 5的表达;而Vit E干预可显著抑制CYP2E1的表达,缓解CYP2E1介导的氧化损伤,有效预防1,2-DCE引起的中毒性脑水肿。 |
关键词: 1,2-二氯乙烷(1,2-DCE) 维生素E(Vit E) 脑水肿 细胞色素P450 2E1(CYP2E1) |
中图分类号: A
文献标识码: R994
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基金项目: 国家自然科学基金(编号:81573105) |
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Protective effect of vitamin E on cerebral edema induced by 1,2-dichloroethane poisoning |
XU Tian-sheng, LUO Chao-hong, JIN Xiao-xia, WANG Gao-yang, ZHAO Feng-hong, JIN Ya-ping
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(Department of Environmental and Occupational Health, China Medical University, Shenyang 110122, China)
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Abstract: Objective To explore the protective effect of vitamin E (Vit E) on cerebral edema induced by 1,2-dichloroethane (1,2-DCE) poisoning.Methods Female Kunming mice were randomly divided into six groups: blank control group, Vit E control group, 1,2-DCE exposed group, and low, middle, high dose Vit E intervention groups. Vit E was continuously given by gavage until the end of the experiment for 4 d, the mice were exposed to 1,2-DCE by static inhalation for 3.5 h and continued for 3 d. Results The results showed that compared with blank control group, the brain tissues of 1,2-DCE exposed mice showed obvious pathological changes of brain edema; water content, MDA level, protein and mRNA expression levels of CYP 2E1 in brain were all significantly increased; the level of GSH, the activity of SOD, CAT,protein and mRNA expressions of Occludin, and protein expression level of Claudin 5 were significantly decreased; while compared with 1,2-DCE exposed group, the water content, MDA level, protein and mRNA expressions of CYP 2E1 in brain were significantly decreased in each intervention group, the level of GSH and expression of CYP 2E1 protein and mRNA of Occludin were significantly increased, the level of GSH,Occudin protein and mRNA were significantly increased,and in middle and high doses intervention groups, the activities of SOD and CAT and the protein expression level of Claudin 5 in brain were significantly increased as well (P<0.05). Conclusion The results suggested that 1,2-DCE exposure could cause brain edema induce expression of CYP 2E1 in brain tissue, induce oxidative damage of brain tissue, destroy its tight junction protein, and inhibit the expression of Occludin and Claudin 5 in mice; while Vit E can significantly inhibit the expression of CYP 2E1, relieve oxidative damage by CYP 2E1, and effectively prevent toxic cerebral edema caused by 1,2-DCE. |
Keywords: 1,2-dichloroethane (1,2-DCE) vitamin E (VitE) cerebral edema Cytochrome P450 2E1 (CYP 2E1) |