N-甲基-D-天冬氨酸Ⅰ型受体在1,2-二氯乙烷急性中毒性脑病中的表达

目的研究N-甲基-D-天冬氨酸Ⅰ型受体(NMDAR1)在1,2-二氯乙烷(1,2-DCE)急性中毒性脑病发病中的作用。方法SD大鼠42只,随机分为1个对照组、3个染毒组和3个染毒后时间观察组,每组6只。染毒组和时间观察组连续静式吸入1,2-DCE 12 h,对照组不接触1,2-DCE和其他化学物。染毒组接触剂量分别为5.0、10.0、20.0 g/m~3,时间观察组接触剂量均为10.0 g/m~3,染毒结束后在干净无毒的环境中分别放置2、4、6 h；NMDAR1在大鼠脑组织中的表达采用免疫组织化学法检测。结果NMDAR1阳性神经元主要分布在大脑皮质和海马。阳性细胞百分比结果：(1)10.0、20.0g/m~3剂量组表达量高于对照组,差异有统计学意义(P＜0.05)。大脑皮质分别为(18.33±1.86)%、(64.17±2.86)%,对照组(1.83±0.75)%；海马分别为(15.5±1.87)%、(47.83±2.16)%,对照组(0.83±0.75)%；(2)时间观察组表达量：大脑皮质2、4、6 h组高于对照组和10.0 g/m~3剂量组,差异有统计学意义(P＜0.05)；表达量分别为(39.07±3.01)%、(70.17±2.93)%、(39.83±2.32)%。海马2、4、6 h组也高于对照组,表达量分别为(16.30±1.03)%、(19.80±1.17)%、(16.50±1.05)%,差异有统计学意义(P＜0.05)；但与10.0 g/m~3剂量组比较,仅4 h组有明显增加,差异有统计学意义(P＜0.05)。结论1,2-DCE急性中毒过程中,NMDAR1表达数量明显上调,兴奋性氨基酸可能通过大量NMDAR1的快速开放参与脑皮质细胞的急性肿胀过程,加重脑水肿的发生。

Expression of N-methyl-D-aspartate receptor-1 in acute intoxicated encephalopathy induced by 1,2-dichloroethane

OBJECTIVE: To study the role of N-methyl-D-aspartate receptor 1 in acute intoxicated encephalopathy induced by 1,2- dichloroethane(1,2-DCE). METHODS: Forty-two Sprague-Dawley rats, which had been randomly divided into 1 control, 3 exposure and 3 after-exposure observation groups were exposed to 1,2-DCE for 12 hr by continual static inhalation except control group. Dosage of exposure groups was 5.0, 10.0, 20.0 g/m(3) on sequence. That of after-exposure observation groups was 10.0 g/m(3). Rats of after-exposure observation groups were observed continually for 2,4,6 hr after exposure. The expression of N-methyl-D-aspartate receptor-1 (NMDAR1) was detected by immunohischemical method. RESULTS: NMDAR1 stained neurons were mainly distributed at cerebral cortex and hippocampus. Compared with that of control group, the percentages of positive cells of NMDAR1 increased evidently at 10.0, 20.0 g/m(3) groups (P < 0.05). They were (18.33 +/- 1.86)%, (64.17 +/- 2.86)% at cerebral cortex, (15.5 +/- 1.87)%, (47.83 +/- 2.16)% at hippocampus. The percentages were also elevated obviously in 2, 4, 6 h after-exposure observation groups. They were (39.07 +/- 3.01)% (70.17 +/- 2.93)% (39.83 +/- 2.32)% at cerebral cortex, (16.30 +/- 1.03)% (19.80 +/- 1.17)% (16.50 +/- 1.05)% at hippocampus; Compared with that of 10.0 g/m(3) group, the percentages increased significantly only in 4 hr group at hippocampus. CONCLUSION: The overactivation of NMDAR1 is the main route by which excitatory amino acids chose to join the development of acute intoxicated encephalopathy induced by 1,2-DCE.