神经干细胞移植脑缺血模型大鼠神经细胞凋亡、分化及神经行为学的变化

Neural stem cell transplantation effects on neuronal apoptosis,differentiation and neurobehavior changes in rats with cerebral ischemia

背景:近年来,神经干细胞移植已成为治疗脑缺血等脑损伤性疾病的研究热点,但机制尚未完全阐明。目的:观察神经干细胞移植治疗脑缺血大鼠对其神经细胞凋亡、分化及神经行为的影响。方法:90只脑缺血模型造模成功SD大鼠随机分为3组,其中模型组30只、磷酸盐缓冲液组(注射磷酸盐缓冲液)30只、神经干细胞组(移植神经干细胞)30只;假手术组30只仅在麻醉状态下分离暴露血管,不进行阻断血流的操作;对照组30只不进行任何操作。对比各组大鼠在造模后第3,7,14天的神经功能评分、脑梗死体积、神经细胞凋亡数、Brdu/Neu N及Brdu/GFAP的表达差异。结果与结论:(1)造模后第7,14天,神经干细胞组大鼠的神经缺损症状评分、脑梗死体积和神经细胞凋亡数均显著低于模型组和磷酸盐缓冲液组(P<0.05),模型组和磷酸盐缓冲液组比较,差异无显著性意义(P>0.05);(2)造模后第3,7,14天,对照组、假手术组的神经缺损症状评分和神经细胞凋亡数均显著低于模型组、磷酸盐缓冲液组和神经干细胞组大鼠(P<0.05);(3)造模后第3天,模型组、磷酸盐缓冲液组和神经干细胞组的Brdu/NeuN阳性细胞计数差异无显著性意义(P>0.05);造模后第7,14天,神经干细胞组的Brdu/NeuN阳性细胞计数均显著高于模型组和磷酸盐缓冲液组(P<0.05),模型组和磷酸盐缓冲液组比较差异无显著性意义(P>0.05);(4)造模后第3,7,14天,神经干细胞组的Brdu/GFAP阳性细胞计数均显著低于模型组和磷酸盐缓冲液组(P<0.05),模型组和磷酸盐缓冲液组比较差异无显著性意义(P>0.05);(5)结果表明,移植神经干细胞治疗脑缺血大鼠可以促进侧脑室下区的内源性神经干细胞向神经元方向分化,减少神经细胞凋亡,改善缺血对大鼠神经功能的损害作用。

BACKGROUND：In recent years, neural stem cell transplantation has become a research hotspot in the treatment of brain injuries, such as cerebral ischemia, but the mechanism has not been fully elucidated.OBJECTIVE：To study the effect of neural stem cell transplantation on neuronal apoptosis and differentiation and neurobehaviors in cerebral ischemia rats.METHODS：Ninety Sprague-Dawley rats with cerebral ischemia were randomized into model group, phosphate buffer solution （PBS） group and neural stem cell group （n=30 per group）. Another 30 rats were selected as sham operation group with vascular exposure but with no occlusion under anesthesia. Thirty normal 30 rats acted as controls with no treatment. Thereafter, neurological deficit scores, cerebral infarction volume, the number of apoptotic nerve cells,BrdU/NeuN and BrdU/GFAP expression were detected at 3, 7, 14 days after modeling.RESULTS AND CONCLUSION：On the 7th day and 14th day after modeling, the neurological deficit scores, cerebral infarct volume and the number of apoptotic nerve cells in the neural stem cell group were significantly lower than those in the model group and PBS group （P 〈 0.05）, but there was no statistically significant difference between the model group and PBS group （P 〉 0.05）. On the 3rd day, 7th day and 14th day after modeling, the neurological deficit scores and the number of apoptotic nerve cells in the control group and sham operation group were significantly lower than those in the model group, PBS group and neural stem cell group （P 〈 0.05）. On the 3rd day after modeling, the BrdU/NeuN positive cell count in the model, PBS and neural stem cell groups showed no statistically significant differences （P 〉 0.05）; on the 7th day and 14th day after modeling, the BrdU/NeuN positive cell count in the neural stem cell group was significantly higher than that in the model group and PBS group （P 〈 0.05）, but the difference between the model group and PBS group was not statistically significant （P 〉 0.05）. On the 3rd day, 7th day and 14th day after modeling, BrdU/GFAP positive cell count in the neural stem cell group was significantly lower than that in the model group and PBS group （P 〈 0.05）,and the latter two groups had no statistically significant difference （P 〉 0.05）. In summary, neural stem cell transplantation for cerebral ischemia contributes to the neuronal differentiation of endogenous neural stem cells in the subventricular zone of the lateral ventricles, reduce neuronal apoptosis, and ease ischemic damage to the rat neurological function.