早期干预改善缺氧缺血性脑损伤大鼠认知能力及其机制分析

CHANGES OF APOPTOTIC NEURONS IN THE BRAIN OF NEONATAL RATS AFTER HYPOXIA-ISCHEMIA AND EARLY INTERVENTION

目的研究早期干预对缺氧缺血性脑损伤(HIBD)大鼠学习记忆功能的影响及其作用机制。方法选用SD大鼠建立宫内HIBD动物模型,随机分为非干预组和干预组,非干预组与正常对照组常规饲养,对干预组采取早期触摸和丰富环境刺激。干预28d后,通过三等臂Y型迷宫试验检测各组大鼠的学习记忆功能,而后取大鼠额皮质和海马组织进行病理观察,并采用DNA缺口原位末端标记法(TUNEL反应法)检测凋亡细胞,观察脑组织神经元凋亡情况。结果单纯HIBD组大鼠学习获得与记忆保持能力明显低于正常对照组(P<0·01),但HIBD干预组Y迷宫测试成绩则优于HIBD非干预组(P<0·01)。同时,HIBD非干预组脑额皮质和海马CA1区神经元缺失远较正常组多(P<0·01),而HIBD干预组与HIBD非干预组之间神经元数量的差异则不那么显著。但HIBD干预组脑额皮质和海马神经元凋亡百分率明显低于HIBD非干预组(P<0·01)。结论早期干预可减轻缺氧缺血性损伤脑组织神经细胞凋亡,该作用可能是早期干预促进HIBD大鼠脑功能修复的机制之一。

Objective To explore the effect of early intervention on functional outcome and neuron apoptosis in the brain of rats with hypoxic-ischemic brain damage （HIBD）. Methods SD rats were used to establish the model of HIBD. The HIBD rats were randomly divide into two groups： non-intervention group and intervention group that received the neonatal handling and was kept in an enriched environment. Non-intervention group and normal control group were kept in a standard condition. On the 28th days after the operation, the learning-memory ability of rats in every group was evaluated throuth tri-equal-arm maze test. Terminal deoxynucleotidyl transferase-mediated dTUP biotinylated nick end labeling （TUNEL） method was used to detect neuron apoptosis in prefrontal cortex and hippocampus of rats. Results Compared with the normal group, the non-intervention HIBD group was significantly decreased in the Y-maze learning ability （P〈0.01）, while the learning-memory ability of the intervention HIBD group was obviously improved （P〈0.01）. The pathology differentiation was obvious between the HIBD groups and the normal controls. The prefrontal cortex and hippocampal CA1 neurons of the HIBD groups were apparently decreased in number as compared with those of the normal controls （P〈0.01）, while the neurons of the HIBD intervention group were a little more than those of the HIBD non-intervention group. At the same time, the percentage of TUNEL positive neurons in prefrontal cortex and hippocampus of the intervention group was less than that of the non-intervention group （P〈0.01）. Conclusion Early intervention can decrease the percentage of apoptotic neurons in the brain of rats with HIBD, which may be one of the mechanisms of early intervention improving the functional outcome of HIBD rats.