单用或联用UDP-糖、GDNF和美金刚对脑白质损伤大鼠长期预后的改善作用

Effects of single or combined application of UDP-glucose, glial cell line derived neurotrophic factor and memantine on long-term prognosis of neonatal rats with periventricular leukomalacia

目的 探讨单用和联用尿苷二磷酸葡萄糖（UDP-糖）、胶质细胞源性神经营养因子（DNF）和美金刚对脑室周围白质软化（PVL）新生大鼠体格发育、学习记忆和肢体运动功能的远期影响。方法5日龄SD新生大鼠按照随机数字表法分为对照组、PVL组、UDP-糖组和UDP-糖＋GDNF＋美金刚组（简称三联药组）。对照组大鼠仅游离右侧颈总动脉，不接扎和缺氧；PVL组大鼠结扎颈总动脉和缺氧；UDP-糖组大鼠在缺血缺氧后给予腹腔注射UDP-糖；三联药组大鼠在缺血缺氧后给予颅内注射GDNF，同时腹腔注射UDP-糖和美金刚。每组大鼠造模前后称重并记录睁眼日龄，在PVL造模后21d进行水迷宫和斜板测试，记录各组大鼠逃逸潜伏期、游泳距离及在不同倾斜角度下的斜板得分。结果 PVL组在各时段的体质量及睁眼日龄均显著低于其他3组，四象限的平均逃逸潜伏期值和游泳距离数值均显著长于其他3组，在45°和50°斜板上的得分均显著低于其他3组，差异有统计学意义（P〈0．05）；两个用药组间以及两个用药组分别和对照组间大鼠体质量、睁眼日龄、逃逸潜伏期值、游泳距离以及斜板评分的差异均无统计学意SL（P〉0．05）。结论 单用UDP-糖或联用UDP-糖、GDNF和美金刚能明显改善脑白质损伤大鼠的长期预后，三联药组的改善作用略微更明显。

Objective To explore the effects of the single or combined application of UDP-glucose, glial cell line derived neurotrophic factor （GDNF） and memantine on the long-term prognosis （physical development, learning and memory and limb function） of rats with periventricular leukomalacia （PVL）. Methods Five-day-old SD rats were randomly divided into the sham-operated group, PVL group, PVL plus UDP-glucose group, and PVL plus UDP-glucose combining GDNF and memantine group （three drugs group）. The rats in the sham-operated group were performed dissociation but not ligation of the fight common carotid artery and given no hypoxia; those in the PVL group were given ligation and hypoxia; those in the PVL plus UDP-glucose group were given intraperitoneal injection of UDP-glucose after ligation and hypoxia and those in the three drugs group were given intracranial injection of GDNF and intraperitoneal injection of UDP-glucose and memantine after ligation and hypoxia. The rats were weighed before and immediately after the establishment of PVL models, and the day age of first time opening eyes was recorded. Both tests of Morris water maze and Rivlin inclined plane were performed in all rats of the 4 groups on 26 day age; the escape latency （EL）, swimming distance and scores in different inclined angle were recorded and compared, respectively. Results The weight at each time interval reduced and the day age of first time opening eyes delayed significantly in the PVL group as compared with those in the sham-operated group, PVL plus UDP-glucose group and three drugs group （/9〈0.05）. The average EL and swimming distance in four quadrants in the PVL group were obviously longer than those in the other 3 groups （P〈0.05）. The scores of inclined plane degrees at 45° and 50° decreased remarkably in the PVL group as compared with those in the other 3 groups （P〈0.05）. No significant differences in the weight, day age of first time opening eyes, values of EL and swimming distance, and scores of inclined plane were observed either between PVL plus UDP-glucose group and three drugs group or between PVL plus UDP-glucose group/three drugs group and sham-operated group, respectively （P〉0.05）. Conclusion The single or combined application ofUDP-glucose, GDNF and memantine can improve significantly the long-term prognosis in rats with PVL; the combined use of UDP-glucose, GDNF and memantine tends to have much obvious improvement in these rats.