摘 要: 目的 探究细胞外信号调节激酶/激活蛋白-1(ERK/AP-1)信号通路在亚急性1,2-二氯乙烷(1,2-DCE)中毒性脑水肿形成中的作用。方法 选取40只健康雌性昆明种小鼠随机分为对照组及3个染毒组;染毒组小鼠于染毒柜中1.2 mg/L 1,2-DCE染毒3.5 h/d,分别染毒1 d、2 d和3 d。染毒结束次日取材,观察脑组织病理切片,测定血清白细胞介素-1β(IL-1β)含量;检测各组小鼠脑组织含水量,MMP-9、Occludin、ERK1/2、p-ERK1/2及AP-1的c-Fos、c-Jun亚基蛋白和mRNA表达水平。结果 染毒2 d和3 d组小鼠出现脑水肿病理改变;与对照组相比,染毒2 d和3 d组小鼠脑组织含水量、MMP-9蛋白和mRNA表达水平上调,Occludin蛋白表达水平降低,差异均有统计学意义(P<0.05);各组ERK1/2蛋白和mRNA表达水平无差别,染毒3 d组小鼠脑组织中p-ERK1/2蛋白、AP-1的c-Fos亚基蛋白和mRNA表达水平及血清IL-1β含量均显著高于对照组(P<0.05);染毒组AP-1的c-Jun亚基蛋白表达水平均高于对照组(P<0.05)。结论 1,2-DCE可通过诱导小鼠血液生成IL-1β,激活小鼠脑组织中ERK/AP-1信号通路上调MMP-9蛋白表达,破坏血脑屏障通透性,参与1,2-DCE中毒性脑水肿形成。 |
关键词: 1,2-二氯乙烷(1,2-DCE) ERK1/2信号通路 激活蛋白-1(AP-1) 白细胞介素-1β(IL-1β) 脑水肿 |
中图分类号: R994.3
文献标识码: A
|
基金项目: 国家自然科学基金(编号:81172644;81573105) |
|
Effect of ERK/AP-1 signaling pathway on brain edema induced by 1,2-dichloroethane |
WANG Ling-xiao,LUO Chao-hong,WANG Gao-yang,ZHAO Feng-hong,WANG Tong,JIN Ya-ping
|
Department of Environmental and Occupational Health,China Medical University,Shenyang 110122,China; NHC Key Laboratory of Hormones and Development,Tianjin Key Laboratory of Metabolic Diseases,Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology,Tianjin Medical University
|
Abstract: Objective To investigate the effect of ERK/AP-1 signaling pathway during the formation of toxic cerebral edema by 1,2-dichloroethane(1,2-DCE)in mice. Methods Forty female Kunming mice were randomly divided into one control group and three poisoned groups. The mice of poisoned groups were given inhalation of 1.2 mg/L 1,2-DCE(3.5 h per day)for 1 d,2 d and 3 d,respectively. The biological materials were taken the next day after poisoning,for observing the pathological sections of brain tissues,detecting the contents of serum IL-1β and brain water,and measuring the expression levels of MMP-9,Occludin,ERK1/2,p-ERK1/2 as well as activator protein-1(AP-1)subunits c-Fos,c-Jun proteins and mRNA in brain tissues. Results The results showed that there were some pathological changes of brain edema observed in mice in 2 d and 3 d 1,2-DCE poisoned groups. Compared with control group,the brain water content and the expression levels of MMP-9 protein and mRNA in mice of 2 d and 3 d 1,2-DCE poisoned groups were significantly increased(P<0.05),the Occludin protein level decreased(P<0.05),there was no significant change in expression level of ERK1/2 protein and mRNA in those groups mentioned above,but 3 d 1,2-DCE poisoned group the expression levels of p-ERK1/2 protein,proteins and mRNA of AP-1 subunits c-Fos,serum IL-1β content as well were all significantly higher than those of control group(P<0.05),additionally,the expression levels of c-Jun protein and mRNA in mice of all poisoned groups were significantly higher than that of control group(P<0.05). Conclusion The results suggested that 1,2-DCE might activate the expression of ERK/AP-1 signaling pathway and up-regulation the expression of MMP-9 by inducing mice blood to produce IL-1β,lead to the increase blood-brain barrier perme- ability,thereby,participate in the formation process of toxic cerebral edema by 1,2-DCE. |
Keywords: 1,2-dichloroethane(1,2-DCE) ERK1/2 signaling pathway activator protein-1(AP-1) interleukin-1β(IL-1β) brain edema |