摘要
目的探讨N-甲基-D-天冬氨酸受体1(NMDAR1)在1,2-二氯乙烷(1,2-DCE)中毒性脑病中的作用机制及NMDAR1非竞争性拮抗剂氯胺酮的干预作用。方法离体培育无特定病原体级新生SD大鼠大脑皮质神经细胞,设对照组、低剂量组、中剂量组、高剂量组和氯胺酮拮抗组,1,2-DCE终浓度分别为0.0、0.5、1.0、2.0和2.0 mmol/L,氯胺酮拮抗组的氯胺酮终浓度为5.0 mmol/L,观察各组神经细胞形态学、超微结构、细胞活力和NMDAR1表达水平的变化。结果与对照组比较,各剂量组神经元和神经胶质细胞形态学以及细胞线粒体、内质网等超微结构均发生不同程度的损伤,细胞活力下降(P<0.01)。氯胺酮拮抗组神经细胞形态学变化和超微结构均较3个剂量组有改善,细胞活力分别高于3个剂量组(P<0.05)。不同染毒处理及不同处理时间的NMDAR1表达水平分别比较,差异均有统计学意义(P<0.01),染毒处理与处理时间的交互效应有统计学意义(P<0.01)。染毒12 h时,低、中、高剂量组NMDAR1表达水平分别高于对照组(P<0.01),氯胺酮拮抗组NMDAR1表达水平分别低于3个剂量组(P<0.01);染毒24 h时,低、中剂量组和氯胺酮拮抗组NMDAR1表达水平分别高于对照组(P<0.01)。结论 1,2-DCE中毒可致离体神经细胞损伤,NMDAR1表达水平增高。NMDAR1在1,2-DCE致神经细胞中毒性脑水肿机制中起到重要作用。氯胺酮可改善1,2-DCE染毒后神经细胞损伤程度。
Objective To study the role of N-methyl-D-aspartate receptor subunit 1 （ NMDAR1 ） in acute intoxicated en-cephalopathy induced by 1,2-dichloroethane （1,2-DCE） and the intervention effect of NMDAR1 non competitive antago-nist ketamine. Methods Nerve cells from SPF SD new born rats were cultured in vitro, which were divided into 5 groups ： control group, low dose group, middle dose group, high dose group and ketamine antagonist group, which were administra-ted with final concentrations of 1,2-DCE at 0. 0, 0. 5, 1.0, 2. 0 and 2.0 mmol/L respectively. The final concentration of ketamine was 5.0 mmol/L in the ketamine antagonist group. The changes of nerve cell morphology, ultrastructure, cell vi-ability and NMDAR1 expression levels were observed. Results Compared with those of the control group, degrees of da- mages were occurred in cell morphology, mitochondria and endoplasmic in 3 exposure groups, and cell viabilities were decreased （P 〈 0. 01 ）. Nerve cell morphology and ultrastructure in ketamine antagonist group were much better than those of each dose group, and the cell viability was higher than that of each dose group （P 〈 0. 05）. There was significant statis- tical differences of NMDAR1 expression among each group with different dose of 1,2-DCE or exposure time （ P 〈 0. 01 ） and statistical significance of interaction between treatment groups and times points was discovered （ P 〈 0. 01 ）. After exposure for 12 hours, NMDAR1 expression levels of each dose group was higher than that of the control group （ P 〈 0. 01 ）, while NMDAR1 expression levels of ketamine antagonist group was lower than each dose group （P 〈0. 01 ）. After 24 hours of exposure, NMDAR1 expression of low dose group, middle dose group and ketamine antagonist group were high-er than those of the control （ P 〈 0.01 ）. Conclusion 1,2-DCE can damage the normal structural morphology of nerve cells, and increase the expression of NMDAR1 in vitro. NMDAR1 plays an important role in acute intoxicated
出处
《中国职业医学》
CAS
北大核心
2014年第1期1-6,共6页
China Occupational Medicine
基金
国家自然科学基金(30271116)
