纳洛酮对血管性痴呆大鼠学习记忆和海马神经细胞内钙离子的影响

Effects of naloxone on learning and memory abilities together with concentration of hippocampal [Ca^(2+) ]_i in rats with vascular dementia

目的:研究纳洛酮对血管性痴呆大鼠空间学习记忆能力的影响及可能机制。方法:结扎双侧颈总动脉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。纳洛酮组于术后立即腹腔注射纳洛酮 0. 8mg·kg-1·d-1,连续 7d。8wk后用Morris水迷宫训练方法,比较 3组间学习记忆能力的差别。用激光共聚焦显微镜观察锥体细胞内钙离子荧光像素值。结果:模型组大鼠隐匿平台逃避潜伏期(EL)比假手术组大鼠明显延长 (P<0. 01),而空间探索实验穿越平台次数明显减少 (P<0. 01 );纳洛酮组大鼠EL较模型组明显缩短(P<0. 01),空间探索实验穿越平台次数明显增加 (P<0. 01)。此外,大鼠海马神经细胞内钙离子荧光像素值模型组(484±299)较假手术组 (135±29 )明显增高 (P<0. 01),而纳洛酮组 ( 139±31 )较模型组明显减低(P<0. 01)。结论:纳洛酮对血管性痴呆大鼠空间学习记忆减退有明显改善,其机制可能是与其防止海马神经细胞内钙离子增高有关。

AIM: To explore the effects of naloxone on spatial learning and memory ability and its possible mechanism for vascular dementia(VD) rats. METHODS: The rats models of vascular dementia were made by permanent bilateral occlusion of both common carotid arteries (2 VO methods). The models were then divided into three groups at random: sham-operated group, model group and naloxone preventive treatment group. Naloxone group was successively received naloxone treatment(naloxone hydrochloride, 0.8 mg·kg -1 ·d -1 , ip) for 7 d after the operation immediately, while the other two groups were received equal volume of saline, ip. All of the rats were trained in Morris Water Maze (MWM) regularly for 5 d to find the escape latencies(EL) after 8 wk of the operation and then followed by a comparison of the learning and memory differnce in three groups. Laser scanning confocal microscope and Fluo-3 were used to measure intracellular calcium fluorescence pixel values of the hippocampal neurons. RESULTS: The EL in model group was significantly longer than that in sham-operated group(P<0.01), but the times of passing through the platform were signicantly decreased(P<0.01). The EL of naloxone group was significantly shorter than that of model group (P< 0.01 ) and the times of passing through the platform were signicantly increased (P< 0.01). Additionally, The fluorescence pixel value of intracellular calcium of hippocampal CA1 region neurons in model group(484±299) was significantly increased (P<0.01); but in naloxone group the fluorescence pixel value of intracellular calcium of hippocampal CA1 region neurons (139±31) was significantly decreased (P< 0.01 ). CONCLUSION: The promoting effects of naloxone on spatial learning and memory deficits in rats with VD are significant. Its mechanism may be connected with the preventing calcium increase in hippocampal neurons by naloxone.