丙泊酚对匹鲁卡品诱发癫痫持续状态大鼠海马NMDA受体2A、2B亚型表达的影响  

Effects of Propofol on the expression of NMDA receptor 2A/2B subunits in hippocampus of status epilepticus rats induced by pilocarpine

作　　者：王恒林[1] 米卫东[2] 王卓强[1] 刘秀珍[1] 张斌[1] 刘艳芹[3] 赵从[3] 王永安[3] 

机构地区：[1]解放军309医院麻醉科,北京100091 [2]解放军总医院麻醉手术中心,北京100853 [3]军事医学科学院毒物药物研究所,北京100850

出　　处：《解放军医学杂志》2010年第5期530-532,536,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金面上项目(30400551)

摘　　要：目的建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发大鼠癫痫持续状态(SE)模型,观察丙泊酚对SE大鼠海马N-甲基-D-天冬氨酸(NMDA)受体亚型(NR2A、NR2B)表达的影响。方法60只SD大鼠随机分为6组(n=10):空白对照(BLK)组、SE组、丙泊酚50mg/kg(PPF)组、安定10mg/kg(DZP)组、东莨菪碱10mg/kg(SCOP)组及MK-801(2mg/kg)组。匹鲁卡品30mg/kg诱发SE模型,惊厥发作程度以Racine分级法判断,反复发作达到4～5级的大鼠纳入实验。待SE发作后30min,各实验组动物分别腹腔注射相应药物,而BLK组和SE组则注射等量生理盐水。24h后取各组大鼠大脑组织,采用免疫组化法检测SE大鼠海马NR2A、NR2B的表达情况。结果SE发作后24h,与BLK组相比,SE组大鼠海马NR2A、NR2B亚型的阳性表达量显著增加(P<0.05);与SE组相比,PPF组海马NR2B表达显著降低(P<0.05),而NR2A亚型表达无明显变化。与SE组相比,MK-801组皮层NR2A、NR2B亚型的表达显著降低(P<0.05),而DZP组、SCOP组的NR2A、NR2B亚型表达无统计学差异。结论丙泊酚对匹鲁卡品诱发大鼠SE的抑制作用可能与其下调NR2B亚型的表达有关。Objective To reproduce pilocarpine induced status epilepticus （SE） model in rats, and investigate the effect of propofol on N-methyl-D-aspartate receptor subunit 2A （NR2A） and 2B （NR2B） in hippocampus of SE rats. Methods Sixty SD rats were randomly divided into 6 groups （10 each）： blank group, SE group, propofol （PPF, 50mg/kg） group, diazepam （DZP, 10mg/kg） group, scopolamine （SCOP, 10mg/kg） group and MK801 （2mg/kg） group. SE was induced by pilocarpine （30mg/kg） in rats except blank group. Convulsion intensity was quantified according to the Racine rating scale. Only onset and recurrent attacks of SE with level 4 to 5 in rats were used in the experiment. Every agent was injected intraperitoneally 30min after onset of SE; equal volume normal saline was injected in the blank group. The rats were sacrificed 24h after injection. Immunohistochemistry was employed to determine the NR2A and NR2B expression in hippocampus of SE rats. Results Immunohistochemistry analysis showed that the expression level of NR2A and NR2B subunits significantly increased 24h after onset of SE in cortices and hippocampus in SE group when compared with that in blank group （P0.05）. However, the expression of NR2B subunit significantly decreased （P0.05）, while of the NR2A subunit nearly unchanged in PPF group compared with that in SE group. The expression of NR2A and NR2B subunits decreased in MK801 group （P0.05）, but unchanged in DZP and SCOP groups when compared with that in SE group. Conclusions Inhibition effect of propofol on SE rats induced by pilocarpine may be attributed to downregulating the expression level of hippocampal NR2B subunit.

关 键 词：二异丙酚 癫痫持续状态 受体 N-甲基-D-天冬氨酸 海马 

分 类 号：R742.1[医药卫生—神经病学与精神病学]