早期干预对未成熟大鼠脑损伤学习记忆及NMDA受体NR1亚单位表达的影响

Influence of early intervention on learning memory ability and expression of NMDA receptor NR1 subunit protein of premature rats with brain damage

目的探讨早期干预对未成熟大鼠脑损伤后学习记忆及NMDA受体NR1亚单位表达的影响。方法选2日龄SD大鼠制作未成熟大鼠脑损伤模型,随机分为丰富环境(EE)组、贫瘠环境(IE)组、标准环境(SE)组,每组20只。另选20只2日龄SD大鼠,仅分离左侧颈总动脉,不予结扎和缺氧,作为对照组(Sham)。EE组于术后第3天行触摸和丰富环境干预,总干预时间为30d。标准环境组和对照组均饲养于标准环境中,不行早期干预。干预结束后行学习记忆能力检测,同时分别于生后第7、35天取各组大鼠海马脑组织免疫细胞化学检测NR1亚单位表达。结果生后5周龄时,EE组学习记忆能力较SE组及IE组明显改善〔逃避潜伏期(ELP):4.75±2.85与12.45±3.23、8.42±2.23比较,空间探索能力:61.36±8.12与50.24±8.29、40.12±7.99比较,P<0.05〕;且丰富环境组海马CA1区NR1阳性反应物着色最强,与标准环境组、贫瘠环境组及对照组比较差异有统计学意义(43.2±6.6与59.5±8.1、88.5±15.5、62.3±9.5比较,P<0.01)。结论早期干预可增强未成熟大鼠脑损伤的学习记忆能力,NMDA受体NR1亚单位表达增多可能是其机制之一。

Objective To investigate the influence of early intervention on learning memory ability and expression of NR1 in premature rats with brain damage. Methods Two days old postnatal of periventricular leueomalacia （PVL） SD rats models were established by the method of SA Back. Then they were used and randomly divided into enriched environment （EE） ,impoverished environment（IE） and standard environment（SE） groups （n= 20）. The sham-operation（sham） rats were served as control group （n= 20）. The neonatal handling and enriched environment intervention were administrated to the EE groups. On 35d, the learning and memory function were evaluated. On 7,35d, the expression of NR1 in the hippocampus was measured by the method of immunohistoehemistry. Results The learning and memory ability （escaped latent period： 4.75 ± 2.85 vs 12.45 ± 3.23 ; 8.42 ± 2.23 ; space learning and memory test： 61.36±8.12 vs 50.24 ± 8.29,40. 1 2 ± 7.99） of EE group were improved compared with SE, IE group（P 〈0.05）. And those abilities of non-intervention group reduced and were much lower than those of sham group. Immunohistochemistry analysis showed that expression of NR1 on 35d in the hippocampus of EE group significantly increased compared with that of SE, IE and sham group （43.2 ± 6.6 vs 59.5 ± 8.1,88.5±15.5,62.3 ± 9.5, P〈0.01）. Conclusion Early intervention can improve learning memory ability in premature rats with brain damage. The enriched environment stimulation could increase the expression of NRI, and it may be mechanism of the recovery of PVL in the premature rats.