美金胺治疗对缺氧缺血性脑损伤新生大鼠长期预后的影响研究

Long-term effects of memantine therapy on neonatal rats with hypoxic-ischemic brain damage

摘要:

目的：动物实验已证明美金胺对缺氧缺血脑损伤具有神经保护作用,但是美金胺治疗能否改善脑缺氧缺血大鼠的长期预后,目前尚无有关研究资料。该研究应用Morris水迷宫测试探讨缺氧缺血后即刻使用美金胺对缺氧缺血性脑损伤新生大鼠长期预后的影响,以期对美金胺的有效性做出全面而客观的评价,为今后建立安全有效的新生儿缺氧缺血性脑损伤的治疗方案提供依据。方法：60只7日龄SD大鼠随机分为对照组、缺氧缺血组(HI组)和美金胺20mg/kg治疗组(治疗组)。各组分别于23日龄始连续5d进行Morris水迷宫测试训练,于28日龄和35日龄正式测试,比较各组的逃逸潜伏期(EL)。结果：28日龄各组EL(s)值分别为:35.1±5.3(HI组)、20.6±3.4(治疗组)以及23.1±21.8(对照组),其中HI组与对照组在EL值之间的差异有显著性(P<0.05)。35日龄各组EL值(s)分别为:35.6±32.3(HI组)、16.3±13.2(治疗组)以及19.7±16.7(对照组),其中HI组与对照组EL值之间的差异有显著性(P<0.05),HI组和用药组则差异有非常显著性(P<0.01)。结论：新生大鼠在脑缺氧缺血后即刻使用美金胺可显著增强其空间辨识和学习记忆功能,改善其长期预后。

Abstract:

OBJECTIVE: Animal trials have demonstrated that memantine has neuroprotective effects on hypoxic-ischemic (HI) brain damage. Whether memantine can improve the long-term prognosis of rats with HI brain damage has not been reported. This study was designed to investigate the long-term effect of memantine therapy on neonatal rats with HI brain damage. METHODS: Sixty postnatal 7-day-old newborn rats were randomly assigned into Normal control, HI and Memantine-treated groups. Memantine (20 mg/kg) was administered immediately after HI in the Memantine-treated group. All subjects received a 5-day training of Morris water maze test from 23 days old. The escape latency (EL) was recorded at 28 and 35 days old. RESULTS: The EL values of the Normal control, HI and Memantine-treated groups at 28 days old were 23.1±21.8, 35.1±5.3, and 20.6±3.4 seconds, respectively. There was a significant difference in the EL value between the HI and the Normal control groups (P<0.05). The EL value of the Normal control, HI and Memantine-treated groups at 35 days old were 19.7±16.7, 35.6±32.3, and 16.3±13.2 seconds, respectively. A prolonged EL induced by HI still existed (P<0.05 vs Normal controls) but memantine treatment shortened the EL (P<0.01 vs HI group) at 35 days old. CONCLUSIONS: Administering memantine immediately after HI can markedly increase the abilities of spatial discrimination, learning and memory and improve the long-term prognosis in rats with HI brain damage.