Wang Gaoyang, Yuan Yuan, Zhang Jun, Gao Lanyue, Tan Xiaoqiong, Yang Guangqian, Lv Xiuqiang, Jin Yaping
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Neurotoxicol Teratol. 2014 Jul-Aug;44:105-12. doi: 10.1016/j.ntt.2014.06.005. Epub 2014 Jun 22.
The aim of this study was to explore the effects of 1,2-dichloroethane (1,2-DCE) on expression of aquaporins (AQPs) and matrix metalloproteinases (MMPs) in the process of brain edema formation. Two parts were included in this study, establishment of animal model of brain edema, and mechanism of brain edema induced by subacute exposure to 1,2-DCE. In part one, mice were exposed to 0, 1.1, 1.2 or 1.3g/m(3) 1,2-DCE, 3.5h per day for 3days. Pathological analysis and water content detection in the brain were examined. In part two, mice were exposed to 1.2g/m(3) 1,2-DCE, 3.5h per day for 1, 2 or 3days, named group D, E and F, respectively. Expression of AQP4, MMP2 and MMP9 in the brain was determined by immunochemical staining, western blot and real time PCR. According to the results of part one, the 1.2g/m(3) dose was chosen for part two, a follow-up time-course study. In part two, protein expression of MMP2 and MMP9 in group F, and AQP4 in group E and F significantly increased compared to the control. Similarly, mRNA levels of AQP4 in group F, and MMP9 in group E and F significantly increased. Our results suggested that exposure to 1,2-DCE might up-regulate the expression of AQP4 protein and MMP9 mRNA at the early phase of brain edema, and AQP4 may play an important role in the brain edema formation.
本研究旨在探讨1,2 - 二氯乙烷(1,2 - DCE)在脑水肿形成过程中对水通道蛋白(AQPs)和基质金属蛋白酶(MMPs)表达的影响。本研究包括两个部分,即脑水肿动物模型的建立以及亚急性暴露于1,2 - DCE诱导脑水肿的机制。在第一部分中,小鼠每天暴露于0、1.1、1.2或1.3g/m³的1,2 - DCE中,每天3.5小时,持续3天。对大脑进行病理分析和含水量检测。在第二部分中,小鼠每天暴露于1.2g/m³的1,2 - DCE中,每天3.5小时,分别持续1、2或3天,分别命名为D组、E组和F组。通过免疫化学染色、蛋白质印迹法和实时PCR测定大脑中AQP4、MMP2和MMP9的表达。根据第一部分的结果,选择1.2g/m³的剂量用于第二部分,即后续的时间进程研究。在第二部分中,与对照组相比,F组中MMP2和MMP9的蛋白表达以及E组和F组中AQP4的蛋白表达显著增加。同样,F组中AQP4的mRNA水平以及E组和F组中MMP9的mRNA水平显著增加。我们的结果表明,暴露于1,2 - DCE可能在脑水肿早期上调AQP4蛋白和MMP9 mRNA的表达,并且AQP4可能在脑水肿形成中起重要作用。