促红细胞生成素对缺氧缺血新生鼠脑损伤学习记忆能力的影响

Effect of erythropoietin on long term learning in neonatal rats with hypoxic-ischemic brain damage

目的研究促红细胞生成素(EPO)对缺氧缺血性脑损伤(HIBD)新生大鼠海马的近期病理改变和远期学习记忆功能的影响。方法新生7d大鼠随机分3组:假手术组、HIBD模型组和HIBD+EPO组。HIBD术后72h观察脑组织病理改变、海马CA1区凋亡抑制蛋白Bcl-2的表达,术后28d评估海马学习记忆功能。结果EPO治疗能显著减轻缺氧缺血侧大脑半球水肿、梗死和出血等病理学改变。免疫组化结果显示HIBD后72h缺血侧海马CA1区Bcl-2蛋白表达量均为HIBD+EPO组>HIBD组>假手术组,3者间比较差异有统计学意义。Morris水迷宫定位航行实验结果显示,5d总平均逃逸潜伏期HIBD组(67.93±7.29)s,HIBD+EPO组(42.95±7.29)s,假手术组(29.67±6.95)s,平均逃逸潜伏期在不同时段和不同实验组之间的差异有统计学意义;空间探索实验示:HIBD组站台周边区域I搜索时间和搜索路程与HIBD+EPO组、假手术组间差异均有统计学意义,而HIBD+EPO组和假手术组间差异无统计学意义,提示HIBD鼠学习记忆能力下降,EPO干预能减轻HIBD对海马学习记忆功能的损害。结论EPO对新生鼠缺氧缺血性脑损伤具有近期病理和远期功能保护作用,其机制与抑制细胞凋亡的发生有关。

Objective To study the effect of erythropoietin （EPO pocampi CA1 area and the long term learning in neonatal rats with ） on pathological changes of hiphypoxic-ischemic brain damage （HIBD）. Methods Seven-day-old Sprague-Dawley rats were randomly divided into 3 groups ; sham-op- erated group, HIBD group and HIBD with EPO treatment （ HIBD ＋ EPO） group. HIBD model was estab- lished by left carotid artery ligation followed by hypoxia with 8% of 02 for 120 min at 7d. HIBD rats received either placebo or EPO （ 1 000 U/kg i. p. qd × 3 ）. Brain histopathology and bcl-2 protein expression at hippocampi CA1 areas were studied 72 h after HIBD. Long term behavioral outcome was assessed by Morris water-maze test 28 days after surgery. Results EPO treatment abated HIBD cerebral edema, necrosis and hemorrhage significantly. Bcl-2 protein expression in hippocampi CA1 was the highest in HIBD ＋ EPO group, and the lowest in sham-operated group. Morris water-maze test showed that 5 days total escape latency in HIBD＋EPO group was shorter than HIBD group, （42.95±7.29） s vs. （67.93 ± 7.29） s, but longer than sham operation group, （29.67 ± 6.95 ） s. Spatial probe test showed that there was significant difference in swimming time group with the other two groups. There was no sham-operated group. Conclusions Exogenous and distance in platform surrounding area 1 in HIBD significant difference between HIBD ＋ EPO group and EPO treatment can significantly decrease brain tissuedamage, prevent learning impairment and decrease apoptosis of neurons in hippocampi CA1 area related to neonatal HIBD.