一次性和连续性灌服乙醇所致实验动物空间辨别和记忆获得障碍及亚力克的预防效应

Preventive effects of ALEC injection on the spatial discrimi-nation and acquired memory disorders induced by once or successive perfusion of ethanol

目的:观察具有抗氧化作用的亚力克对一次性灌服和连续灌服乙醇所致实验动物空间辨别和记忆获得障碍的预防作用。方法:实验于2004-06/08在泰山医学院基础医学研究所完成。①Morris水迷宫法:取SD大鼠40只,随机分为生理盐水组、乙醇组、亚力克高、中和低剂量组5组,每组8只。生理盐水组和乙醇组腹腔注射等量生理盐水;亚力克高、中和低剂量组分别腹腔注射亚力克犤由α-亚麻酸、L-赖氨酸、维生素E和维生素C(432:187:18:8)组成犦1.6,0.8,0.4mL/kg,连续给药11d,在第11天给药前除生理盐水组外其余4组一次性灌服体积分数为0.5的乙醇5mL/kg后立即给药,给药后1h测试逃避潜伏期和目标区逗留的时间比值。②Y型电迷宫法:取昆明种小鼠40只,随机分为生理盐水组、乙醇组、亚力克高、中和低剂量组5组,每组8只。生理盐水组灌服生理盐水;其余4组连续30d灌服体积分数为0.5的乙醇0.06mL/kg。测试小鼠每天的错误次数和反应时间。③避暗法:取昆明种小鼠40只,分组及给药方法同②。测试小鼠的避暗潜伏期、错误次数和受电击时间。结果:40只大鼠和80只小鼠均进入结果分析,无脱落。①亚力克对一次性灌服乙醇所致大鼠空间辨别障碍的预防作用:乙醇组在目标区逗留的时间占总时间的比值显著低于生理盐水组、亚力克高、中、低剂量组(0.22±0.02,0.40±0.08,0.32±0.03,0.36±0.11,0.31±0.04)。②亚力克对连续灌服乙醇所致小鼠空间辨别障碍的治疗作用:亚力克高剂量组的错误次数少于亚力克中、低剂量组和乙醇组犤(1.9±1.3,3.1±1.2,3.7±2.0,5.8±1.7)次犦。亚力克高剂量组的反应时间短于亚力克中、低剂量组和乙醇组犤(2.7±1.3,3.7±1.5,2.6±2.7,12.8±4.6)s犦。③亚力克对连续灌服乙醇所致小鼠记忆获得障碍的治疗作用:亚力克高剂量组的错误次数少于亚力克低剂量组和乙醇组犤(1.7±1.1,2.3±1.5,4.2±2.2)次犦。亚力克高剂量组的电击时间短于亚力克中、低剂量组和乙醇组犤(1.2±0.9,1.4±0.6,1.6±0.4,3.0±0.8)s犦。结论:①一次性灌服乙醇可明显干扰大鼠的空间学习及记忆再现能力,预先给予亚力克能明显减轻乙醇对此的损害作用。②连续灌服乙醇可造成小鼠空间学习能力下降和避暗作业中的记忆获得障碍,亚力克对记忆障碍有明显改善,且具有量效关系,最高剂量组治疗效果最好。

AIM： To observe the preventive effects of ALEC injection, which has the anti-nxidation, on the spatial discrimination and memory disorders induced by once or successive perfusion of ethanol. METHODS： The experiment was earried out in the Institute of Basic Medicine of Taishan Medical College, between April and August 2004. ①Morris water-maze test： Forty SD rats were randomly divided into saline group, ethanol group, ALEC high, middle and low dosage groups with 8 rats in each group. Hats in the saline group and ethanol group were injected intraperitoneally with saline of the same volume, and those in the ALEC high, middle and low dosage gronps were treated with intraperitoneal injection of ALEC （1.6, 0.8, 0.4 mL/kg）,which consisted of α-linolenic acid, Llysine, vitamin E and C] for 11 continuous 11 days. On the 11th day, except saline group, the rats in the other 4 groups were perfused with 5 mL/kg ethanol （volume fraction was 0.5） all at ,once before administration, and the ratio of escape latency to stayed length in the objective area was determined at t hour after administration. （2） Y-maze test： Forty Kunming mice were randomly divided into saline group, ethanol group, ALEC high, middie and low dosage groups with 8 mice in each group. Mice in the saline group were perfused with saline, and those in the other 4 groups were treated with perfusion of 0.06 mL/kg ethanol （volume fraction was 0.5） for 30 continuous days. The mistake times and reaction times every day were tested. （3） Darkness avnidance test： Forty Kunming mice were used, the grouping anct administration were the same as those mentioned in step ②. The darkness avoidance latency, mistake times and electric shocked time were measured. RESULTS： All the 40 rats and 80 mice were involved in the analysis of results. ①The preventive effects of ALEC injection on the disorder of spatial diserimination induced by once perfusinn of ethanoh The ratio of the stayed length in the objective area to the total duration was significantly lower in the ethanol group than in the saline group, ALEC high, middle and low dosage grnnps （0.22±0.02, 0.40±0.08, 0.32±0.03, 0.36±0.11, 0.31±0.04）. （2） The therapeutic effects of ALEC injection on the disorder of spatial discrimination induced by socccessive peffusion of ethanol： The mistake times in the ALEC high dosage group was less than those in the ALEC middle and low dosage groups and ethanol group [（1.9±1.3, 3.1±1.2, 3.7±2.0, 5.8±1.7） times]. The reactiun time in the ALFC high dosage group was less than those in the ALEC middle and low dosage groups and ethanol group [（2.7±1.3, 3.7±1.5, 2.6±2.7, 12.8±4.6） s].③ The therapeutic, effects of ALEC on the memory disorders induced by successive perfusion of ethanol [（1.7±1.1, 2.3±1.5, 4.2±2.2） times]. The electric shocked time in the ALEC high dosage group was less than those in the ALEC middle and low dosage groups and ethannl group 1（1.2±0.9, 1.4±0.6, 1.6±0.4, 3.0±0.8） s]. CONCLUSION：① Once perfusion of ethanol can obviously obstruct the spatial learning and memory reneeurrenee abilities, pre-administration of ALEC can apparently relieve the ethamol-induced damages.② Successive perfusion of ethanol can lead to the decrease of spatial learning ability anct the memory disnrders in darkness avoidance, ALEC can obviously improve the memory disorder in a rinse-effect manner, and the therapeutic： effect is the best in the highest dosage group.