新生大鼠低氧缺血性脑损伤对脑组织病理形态和神经营养因子的影响

Effects of hypoxic-ischemic brain injury on cerebral pathology and neurotrophic factor in neonatal rats

目的改进新生大鼠低氧缺血性脑损伤(HIBI)模型的制作方法,观察低氧缺血对脑组织病理形态和神经营养因子的影响。方法大鼠随机分为空白对照组(n=5)、假手术组(n=8)和HIBI模型组(n=19),HIBI模型制作中省去了经典Rice法中的麻醉步骤和动物手术后休息时间,观察HIBI后大鼠体重增长情况,行为能力表现以及脑组织病理形态学改变;比较HIBI制模后3 d假手术组及HIBI组鼠脑匀浆beta-NGF和human-NT3的变化。结果 (1)HIBI模型组体重增长明显落后于空白对照组和假手术组(P<0.01);(2)HIBI组全部出现不同程度的行为异常:84%翻身不能,63%肌肉颤动和/或头颤,抽搐者占42%,死亡率为21%。制模后3 d HIBI模型组大鼠的行为障碍和异常运动的发生率均明显低于制模当日(P<0.01);(3)HE染色可见HIBI模型组大鼠左侧大脑半球神经元损伤及神经胶质细胞增生;(4)制模后3 d鼠脑匀浆human-NT3含量较假手术组增加(P<0.05);β-NGF含量无明显变化。结论制作的新生大鼠HIBI模型更符合临床新生儿HIBI的自然病程。HIBI早期神经营养因子表达增加在神经保护机制中发挥重要作用。

Objective To improve a model of hypoxic-ischmic brain injury （HIBI） in neonatal rats and observe the effects of hypoxic-ischemic brain injury on cerebral pathology and neurotrophic factor. Methods Thirty-two healthy 7- day-old neonatal Sprague-Dawley （SD） rats were used as research subjects and randomly divided into 3 groups： the control group （n =5）, the sham operated group （n =8）, and the HIBI group （n = 19）. The rats in the HIBI group received hy- poxia immediately after operation without previous anaesthesia. The body weight, behavioral ability and neuropathological changes in each group were observed. β-NGF and human-NT3 of the brain tissue in the sham operated and HIBI groups were compared on d3 and d14. Results （ 1 ） The body weight gain of the HIBI group was significantly slower and lower than that in the control group and sham operated group （P 〈 0.01 ）. （2） Behavioral abnormalities were found in all rats of the HIBI group including unable to turnover （84%）, muscle tremor and/or head tremble （63%） and mortality （21%）.（3） HE staining showed neuronal damages and proliferation of neuroglial cells in the left hemisphere of the HIBI group. （4） The concentration of human-NT3 in the HIBI group was increased than that of sham operated group, but the concentra- tion of β-NGF was not significantly different from that in the two groups on d3. Conclusions A neonatal rat model of HIBI is successfully established and it is more closely resembling the course of human neonatal HIBI. The increase of neurotro- phic factor plays an important role in the neuroprotection mechanism in the early phase of HIBI.