纳洛酮对血管性痴呆大鼠学习记忆能力和海马神经细胞内钙离子浓度的影响(英文)

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

背景:脑缺血时阿片受体发生变化并可导致痴呆,阿片受体拮抗剂纳洛酮对脑缺血时阿片受体变化起调控作用,故纳洛酮对血管性痴呆可能起预防作用。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减退的防治作用,探讨防治作用的神经机制。主要涉及海马神经细胞内钙离子浓度。设计:随机对照的实验研究。地点和对象:在汕头大学医学院清洁级实验动物饲养中心,30只雄性SpragueDawley大鼠。采用持久性结扎双侧颈总动脉方法制备血管性痴呆模型,随机分为假手术对照组、模型组和防治组。干预:防治组于术后即连续7d腹腔注射纳洛酮,其他两组腹腔注射等体积生理盐水。8周后用Morris水迷宫训练方法。主要观察指标:假手术对照组、模型组与防治组大鼠的隐匿平台逃避潜伏期,空间探索实验穿越平台次数,可见平台实验逃避潜伏期。三组钙离子荧光像素值。结果:假手术组和防治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犤假手术组为(7.80±4.70)s,防治组为(8.10±2.93)s,模型组为(21.26±17.41)s,F=15.028,P<0.01犦,前两者差异无显著性意义(P>0.05);空间探索实验穿越平台次数明显增加犤假手术组为(8.45±1.19)次/min,防治组为(8.00±1.17)次/min,模型组为(4.44±1.74)次/min,F=23.257,P<0.

BACKGROUND:The alteration of opioid receptor during cerebral ischemia can induce dementia.Naloxone, opioid receptor antagonist,can modulate the alteration of opioid receptor during cerebral ischemia and thereby it may have preventive effects on vascular dementia(VD).OBJECTIVE:To investigate the preventive effects of naloxone on spatial learning and memory deficits in rats with VD for the discussion on its neural mechanism, mainly involving the i in hippocampal neurons.DESIGN:A randomised controlled trial.SETTINGS and MATERIALS:VD model was established in 30 male Sprague Dawley(SD) rats in a cleanness grade selected from the Experimental Animal-feeding Centre of the Medical College of Shantou University by permanent ligation in common carotid artery on both sides.Rats were randomly allocated into sham-operation group, model group and naloxone group.INTERVENTION:Naloxone was injected intraperitoneally and continuously for 7 days after model establishment in naloxone group and same amount of saline was injected intraperitoneally in the other two groups.Morris water maze(MWM) training method was used after 8 weeks.MAIN OUTCOME MEASURES:The escape latency(EL) of submerged platform training,platform crossing times in spatial exploration experiment, the escape latency of visible platform training in rats of three groups, and the fluorescence pixel of the Ca2+in the three groups under the laser scanning confocal microscope. RESULTS:The EL of MWM submerged platform training in rats of sham-operation group[(7.80±4.70) s] was significantly shortened compared with that of naloxone group and model group[(8.10±2.93) s and (21.26±17.41) s,respectively](F=15.028,P< 0.01), but there was no significance between sham-operation and naloxone group (P >0.05);The platform crossing times in spatial exploring experiments of the rats in sham-operation group[(8.45±1.19)/minute] significantly increased compared with that of naloxone and model group[(8.00±1.17)/minute and(4.44±1.74)/minute, respectively](F=23.257,P< 0.01) but there was no significance between sham-operation group and naloxone group(P >0.05).There were no significant differences of the latencies of visible platform training among three groups(P >0.05).The mean value of fluorescence pixel of the sham-operation group was 135.05±29.14;Naloxone group was 139.39±30.74;The model group was 484.05±298.72, significantly higher than that of other groups(P< 0.01,F=26.363).CONCLUSION:Naloxone has significant preventive effects in spatial learning and memory deficits in VD rats.Its mechanism may be related to naloxone preventes the increase of the intracellular Ca2+in hippocampal neurons.