摘要
目的研究胆碱酯酶抑制剂VX中毒大鼠学习记忆能力的变化以及宾赛克嗪的救治作用。方法♂Wistar大鼠,随机分为正常对照组、VX模型组、宾赛克嗪0.5、1.5、4.5mg·kg-1治疗组;模型组皮下注射VX(1×LD50),正常组给予等剂量生理盐水,各治疗组在VX染毒后5min腹腔注射给予相应药物救治。在染毒后4h分离海马,用透射电镜观察神经元的变化;在给药后d8采用Morris水迷宫试验对各组动物进行学习记忆功能检测,包括定位航行实验、空间探索实验和翻转实验。结果①定位航行实验及翻转实验表明:模型组大鼠逃逸潜伏期和游程较正常组明显延长(P<0.05或P<0.01),学习记忆能力明显降低;空间探索实验表明:正常组动物在目标象限的时间和游程明显高于其余象限(P<0.01),而模型组动物在目标象限的时间和游程与其余象限无差别,空间探索能力降低;宾赛克嗪0.5、1.5、4.5mg·kg-1治疗组能缩短染毒大鼠逃逸潜伏期和游程,在目标象限的时间和游程均高于其他象限,改善甚至逆转染毒大鼠学习记忆能力的降低。②染毒后4h,模型组的大鼠海马神经元超微结构破坏,出现空泡样变,核固缩,细胞器匀质化;宾赛克嗪0.5、1.5、4.5mg·kg-1治疗组对神经元具有保护作用,宾赛克嗪4.5mg·kg-1治疗组可完全逆转海马神经元的病理损伤。结论胆碱酯酶抑制剂中毒时,大鼠学习记忆功能下降;宾赛克嗪能改善大鼠学习记忆功能,与其能保护中毒时海马神经元病理损伤有关。
Aim To investigate the functional changes of the learning and memory induced by cholinesterase inhibitor VX poisoning and the therapeutic effect of benthiactzine. Methods Wistar rats were randomly divided into five groups： control group, VX poisoning （model） group, benthiactzine 0. 5,1.5,4. 5 mg· kg^- 1 groups. The above mentioned drugs were respectively given（ip）5 min after VX poisoning at the dose of 1×LD50 （sc）. The morphological changes of the neurons in hippocampus were determined by electron microscope at 4 hours after VX poisoning; the function of learning and memory was measured by Morris water maze test 1 week after exposure to VX, including place navigation test, spatial probe test and transfer test. Results （1） Escape latency and path length in model group were significantly increased compared with those of control group during the place navigation test and transfer test （P 〈0.05 or P 〈 0.01）,which indicated that the function of learning and memory in rats was decreased after exposure to VX;control rats spent more time and swam a longer distance in the training quadrant than in the other three quadrants during the transfer test, in marked contrast, the time spent and the distance swum was equal in each of the four quadrants by model rats,which indicated that the function of spatial probe in rats was decreased after exposure to VX. Escape latency and path length were significantly shortened compared with those of model group, and the time spent and the distance swum were similar to control group after administration of benthiactzine at dose of 0. 5,1.5, 4.5 mg · kg^-1. The decrease of learning and memory in model rats could be improved or totally reversed after benthiactzine administration. （2） The neurons injury in hippocampus was obvious at the 4 hours after VX poisoning by electron microscope, including karyopycnosis, apomorphosis of endocytoplasmic reticulum, and organelles damage. These pathological changes could be improved dose-dependently after benthiactzine
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第10期1282-1286,共5页
Chinese Pharmacological Bulletin
基金
国家重大新药创制科技重大资助专项(No2009ZXJ09002-014
2009ZX09301-002)
关键词
胆碱酯酶抑制剂
学习记忆
宾赛克嗪
海马
水迷宫
中毒
cholinesterase inhibitor
learning and memory
benthiactzine
hippocampus
water maze
poisoning
