酒精性痴呆大鼠模型的建立方法及评价

The evaluation of different methods establishing alcohol-associated dementia rat model

目的通过比较不同酒精作用途径、剂量和时间对学习记忆功能的影响,寻求酒精性痴呆(alcoholassociated dementia,AAD)动物模型的最佳建立方法。方法以SD大鼠为实验对象,选择不同剂量酒精(20%,4～12mL/kg)连续腹腔注射和灌胃,持续周期为14d和28d,并以Morris水迷宫行为学检测、大鼠海马组织形态学变化和神经细胞凋亡检测作为AAD动物模型的评价标准。结果与生理盐水灌胃组〔(5.68±1.30)s〕相比,大鼠在给予低剂量酒精(4mL/kg)灌胃14d后,其逃避潜伏期时间显著延长〔(24.70±5.43)s,P<0.05〕,提示其学习记忆功能受损害;而高剂量(12mL/kg)酒精灌胃组其逃避潜伏期虽有延长趋势〔(9.55±2.30)s〕,但无统计学差异。与生理盐水腹腔注射组〔(5.31±0.85)s〕相比,酒精腹腔注射组大鼠的逃避潜伏期时间亦延长〔(12.49±2.82)s,P<0.05〕。低剂量酒精灌胃可诱导大鼠海马形态结构改变以及促使神经细胞显著凋亡,但高剂量酒精灌胃和酒精腹腔注射组改变不明显。结论酒精灌胃可诱导大鼠学习记忆功能明显损害,是ADD建模的适宜方法,但酒精剂量不宜过高。

Objective To find the best way for setting up an alcohol-associated dementia （AAD） rat model by comparing the effect of different alcohol administration approaches, alcohol doses and treat time on rats learning and memory function. Methods SD rats were intragastricly/intraperitoneally administrated with different doses of ethanol for 14/28 days. Then these models were evaluated by observing Morris Maze behavior, hippocampus morphology and neuron apoptosis. Results Compared with the saline-intragastric control group [ （5.68±1.30） s], the escape latency （EL） time of rats receiving ethanol intragastric-administration （4 mL/kg） for 14 days was apparently prolonged [ （24.70±5.43） s, P〈0.05], which suggested the learning and memory function of rats have been impaired by ethanol administration. However, ethanol intragastric-administration with high dose （12 mL/kg） had little effects on the EL time of rats [（9.55±2.30） s, P〉0.05], there was no statistical difference. Compared to the saline-intraperitoneal control group [ （5. 31±0.85） s], the EL time of rats treated with ethanol intraperitoneal-injection for 14 days was also extended [（12.49±2.82） s, P〈0.05]. In addition, our results indicated that the morphological structure was apparently damaged and notable neuron apoptosis was induced in rat hippocampus after low dose of ethanol-intragastric administration, but not for high dose of ethanol-intragastric administration or ethanol-intraperitoneal administration. Conclusions The learning and memory function of rats is apparently damaged by ethanol intragastric-administration, which is suitable for setting up AAD rat model, but the dose of ethanol should not be too high.