【摘要】 目的观察右美托咪定对脑缺血缺氧新生大鼠神经凋亡以及对神经功能和长期学习记忆能力的影响。方法 7天龄SD大鼠90只。建立大鼠(7d)脑缺血缺氧损伤(hypoxic-ischemic encephalopathy,HIE)模型。假手术组(S)仅进行手术而不造成缺氧状态;HIE模型组(R)持续缺氧2h;右美托咪定25μg/kg组(D1)、右美托咪定50μg/kg组(D2),于HIE 2h后,即刻分别静脉注射右美托咪定25μg/kg、50μg/kg;育亨宾组(Y),于HIE 2h后,即刻静脉注射给予右美托咪定50μg/kg和育亨宾5μg。Western blot法检测各组干预后24h,caspase-3表达和新生大鼠神经功能评分;干预后4周后,Morris水迷宫检测学习记忆能力的变化。结果干预后24h,R组caspase-3表达和神经功能评分明显高于S组,D1组、D2组和Y组低于R组,Y组高于D1组和D2组,差异均有统计学意义(P<0.05)。干预后4周后,Morris水迷宫逃避潜伏期第1~5天逐渐缩短,差异均有统计学意义(P<0.05)。第1天各组逃避潜伏期差异无统计学意义(P>0.05);第2、3、4、5天,R组逃避潜伏期较S组延长,D1组、D2组、Y组较R组缩短,Y组长于D1组、D2组,差异均有统计学意义(P<0.05)。R组目标像限停留时间明显少于S组,D1组、D2组、Y组明显多于R组,Y组少于D1和D2组,差异均有统计学意义(P<0.05)。D1与D2组神经功能评分、caspase-3表达、水迷宫检测差异均无统计学意义。结论脑缺血缺氧导致新生大鼠脑海马组织神经元凋亡增多,远期新生大鼠学习记忆能力降低;右美托咪定25μg/kg、50μg/kg均抑制caspase-3表达,减少神经元的凋亡,并改善新生大鼠远期学习记忆能力。更多还原

【Abstract】 Objective To observe the effect of dexmedetomidine on neuronal apoptosis in neonatal rats with cerebral ischemia and hypoxia,and to explore the effect of dexmedemidine on neurological function and long-term learning and memory ability.Methods Hypoxic-ischemic encephalopathy(HIE)was built for the model of cerebral ischemia and hypoxia.Ninety sevenday-old(P7)Sprague-Dawley rats were randomized into five groups:sham operation group(S),the HIE group(R),the dexmedetomidine(25μg/kg)group(D1),the dexmedetomidine(50μg/kg)group(D2),the yohimbine group(5μg)(Y).P7 rats were operated without hypoxia in S group,and continued hypoxia for 2hin R group.After HIE 2h,P7 rats were pretreated with different concentrations of dexmedetomidine(25μg/kg,)in D1 group,and pretreated with dexmedetomidine(50μg/kg)in D2 group and yohimbine(5μg)in Y group.After 24 h,the expression of caspase-3 was detected. Neurological deficit scores were used to evaluate neurological function.For 4 weeks after the intervention,Morris water maze test was used to evaluate the changes in learning and memory ability.Results HIE in R group induced the upregulation of caspase-3 and neurological deficit scores,compared with S group(P<0.05).Dexmedetomidine(25μg/kg,50μg/kg)and yohimbine pretreatment markedly down-regulated the expression of caspase-3and neurological deficit scores,compared with R group(P<0.05).The escape latency of R group was increased compared with S group,and reduced with D1,D2,Y group at 2th,3th,4th and 5th day after training(P<0.05).The escape latency of both D1 and D2 group were reduced at 2th,3th,4th and 5th day,and increased time of target quadrant compared with R group,and reduced compared with S group(P<0.05).Neurological deficit scores and the expression of caspase-3were significantly reduced in Y group compared with D1 and D2 group(P<0.05).There were not significant differences between D1 and D2group in neurological deficit scores,the expression of caspase-3and Morris water maze test.ConclusionHIE causes neuronal apoptosis in the hippocampus of neonatal rats,and decrease the ability of learning ang memory in long-term neonatal rats.The expression of caspase-3 was inhibited by dexmedetomidine pretreatment(25μg/kg,50μg/kg),which reduced the apoptosis of neurons.Dexmedetomidine treatment for neonatal rats during HIE could improve the long-term learning and memory ability of neonatal rats.更多还原