目的 研究神经生长因子（NGF）对缺血缺氧性脑损伤大鼠学习记忆能力的影响。方法 选取30只21 d龄的雄性SD大鼠，随机分为假手术组、模型组和NGF干预组，利用左侧颈动脉结扎结合低氧环境建立缺血缺氧性脑损伤模型，以大鼠出现左旋、翻身和衡异常则为造模成功。NGF干预组于造模成功后次日通过大鼠立体定位仪icv NGF溶液，40 μg/kg，2次/周，共处理4周，模型组和假手术组给予等量生理盐水注射。采用BBB评分、悬吊试验、斜坡试验评价大鼠四肢运动能力，水迷宫实验评价大鼠定位航行和空间探索实验学习记忆能力，并取脑组织皮质区进行HE染色观察其病理变化。结果 NGF干预后大鼠的BBB评分、悬吊试验时间提高，而斜坡试验时间缩短，差异有统计学意义（P<0.05）；NGF干预后大鼠找到平台时间和定位航行中潜伏期、游泳距离缩短，在第I象限和中环停留的时间延长，且差异具有统计学意义（P<0.05）。HE染色结果显示，与假手术组相比，模型组大鼠皮质区神经细胞排列紊乱且数目明显减少，并可见炎性细胞浸润，部分出现变性和坏死，而NGF干预后神经细胞排列紊乱及神经细胞数目减少明显改善，变性及坏死细胞数目也明显较少。结论 NGF可能是通过改善缺血缺氧性脑损伤模型大鼠神经功能损伤，使神经组织功能恢复，从而提高了神经运动及学习记忆能力。

Objective To study the effects of nerve growth factor (NGF) on learning and memory abilities of rats with hypoxic-ischemic brain damage. Methods Thirty male SD rats aged 21 d old were enrolled and randomly divided into sham operation group, model group, and NGF intervention group. Hypoxic-ischemic brain damage models were established by left carotid artery ligation combined with hypoxic environment. If there was levorotation, turning over and abnormal balance, the modeling was successful. NGF intervention group was injected with NGF solution 40 μg/kg twice a week in the lateral ventricle for 4 weeks on the next day after the successful modeling. Model group and sham operation group were injected with normal saline. BBB score, suspension test, and slope test were applied to evaluate motor ability of rats. Water maze test was applied to evaluate learning and memory ability in place navigation and space exploration experiments. The cortical area of brain tissue was taken to observe pathological changes by HE staining. Results After NGF intervention, BBB score and time of suspension test were increased, while time of slope test was shortened (P < 0.05). After NGF intervention, time of rats finding out platform, latency and swimming distance in place navigation were shortened, staying time in the first quadrant and the middle ring was prolonged (P < 0.05). The results of HE staining showed that compared with sham operation group, arrangement of nerve cells in cortical area was disordered, and their number was significantly reduced in model group. There was inflammatory cell infiltration, and some were accompanied with degeneration and necrosis. After NGF intervention, disordered arrangement of nerve cells and decreased nerve cells number were significantly improved, and number of degeneration and necrosis cells was also significantly less. Conclusion NGF may recover nerve tissue function by improving nerve function damage in cerebral palsy rats, thus improve nerve motor, learning and memory ability.

R971

河南省卫生计生科技项目（2018077）