纳洛酮对血管性痴呆大鼠学习记忆能力的影响及其胆碱能机制

目的 研究阿片受体拮抗剂纳洛酮对血管性痴呆大鼠空间学习记忆能力的影响及其胆碱能机制。方法 采用持久性结扎双侧颈总动脉方法制备血管性痴呆模型,随机分为假手术组、模型组和纳洛酮组。纳洛酮组手术后即连续7d腹腔注射纳洛酮。8周后用Morris水迷宫训练方法,比较三组大鼠的空间学习记忆能力的差异,观察纳洛酮对血管性痴呆大鼠空间学习记忆减退的防治作用。免疫组化和计算机图像分析技术定量检测CA1区CHAT表达。结果假手术组和纳洛酮组与模型组的实验大鼠相比,其Morris水迷宫隐匿平台逃避潜伏期明显缩短(P<0.01),前两组无显著性差异(P>0.05);空间探索实验穿越平台次数明显增加(P<0.01),前两组无显著性差异(P>0.05)。可见平台实验逃避潜伏期三组间无显著性差异(P>0.05)。CA1区CHAT表达的阳性单位数、灰度值模型组较假手术组减少(P<0.01);纳洛酮组与假手术组无明显差异(P>0.05)。结论纳洛酮对血管性痴呆大鼠空间学习记忆减退有明显防治作用。其机制可能是与纳洛酮抑制CHAT活性降低或增加海马缺血后降低的CHAT活性有关。

Effects of naloxone on spatial learning and memory deficits in rats with vascular dementia and its choliner gic mechanism

Objective To study the preventive effects of naloxone, a general competitive opioid receptor antagonist, on spatial learning and memory deficits in rats with vascular dementia ( VaD) . Methods The rats model of vascular dementia were made by permanent bilateral occlusion of both common carotid arteries (2-VO methods) ,the models were divided into three groups at random:sham-operated group,model group and naloxone group. The latter group successively received naloxone treatment (naloxone hydrochloride, 0. 8mg/kg, i. p. ) for7days after the operation immediately, while the former two groups were received equal volume saline injected intraperitone-ally. All of the rats were trained in Morris water maze orderly for Sdays to find the escape latencies. Immunohisto-chemistry and computerized technique were applied to quantitatively analyze the expression levels of CHAT activity in hippocampal CA1 regions pyramidal cells. Results The escape latencies in model group rats were significantly longer than that in sham-operated(P<0. 01) , there is no significant difference between naloxone group and sham-operated group( P>0. 05) ;the times of passing through the platform were significantly increased( P<0. 01) ,there was no significant difference between the former two groups(P>0. 05). The latencies were no significantly difference among the three groups in the visible platform task training ( P > 0. 05 ) . The number of positive units of CHAT activity expression and the grade of gray value in hippocampal CA1 region in model group were significantly less than that in sham-operated and naloxone group( P<0. 01) ; there were no significant differences in number of positive units and grade of gray value between the latter two groups ( P > 0. 05). Conclusions The preventive effects of naloxone on spatial learning and memory deficits in rats with VaD are significant. Its mechanism may be related to naloxone suppressed CHAT activity decrease or increased the decreased CHAT activity after cerebral ischemia in hippocampal CA1 region.