Olig2 knockdown alleviates hypoxic-ischemic brain damage in newborn rats.
Olig2 knockdown alleviates hypoxic-ischemic brain damage in newborn rats.
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DOI：
10.14670/hh-18-344
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发表时间：
2021-05
影响因子：
2
通讯作者：
L. J. Yang;H. Cui
中科院分区：
文献类型：
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作者：
L. J. Yang;H. Cui
目的神经元损伤是新生儿缺氧缺血性脑损伤（HIBD）的重要病理机制。我们在之前的研究中发现，少突胶质细胞转录因子2 （Olig2）的下调能够提高大脑细胞的存活率。不过，具体机制尚未明确。方法将3 d龄sd大鼠随机分为正常对照组、Olig2-RNAi组和rnai阴性对照组。正常对照组不给予治疗，Olig2-RNAi组给予Olig2 RNAi腺病毒，RNAi阴性对照组在HIBD模型完成后给予对照腺病毒。腺病毒局部注射完成后3 d，用三苯基四氮唑（TTC）染色观察梗死灶及其体积。模型建立7 d后用苏木精-伊红染色法观察组织状态，用天蓝色亚甲基蓝染色法测定细胞活力。透射电镜观察亚细胞损伤。采用旋转杆分析检测运动行为能力，采用MWM法评价记忆。结果TTC染色显示，Olig2-RNAi组脑损伤面积小于rnai阴性对照组。苏木精-伊红染色显示HIBD后海马区存在严重的细胞损伤，Olig2敲除后有所改善。蓝色亚甲基蓝染色和电镜结果显示，敲除Olig2后细胞得到改善。与Olig2-RNAi阴性对照组相比，大鼠在旋转杆上停留时间更长，水迷宫实验潜伏期逐渐缩短。结论Olig2基因敲低可促进新生大鼠缺氧缺血性脑损伤的修复。
OBJECTIVES Neuronal damage is an important pathological mechanism in neonatal hypoxic-ischemic brain damage (HIBD). We found in our previous studies that oligodendrocyte transcription factor 2 (Olig2) downregulation was able to increase cell survival in the brain. However, the specific mechanism has yet to be clarified. METHODS Sprague-Dawley rats aged 3 d were randomly divided into three groups: the normal control group, the Olig2-RNAi group, and the RNAi-negative control group. The normal control group received no treatment, the Olig2-RNAi group received the Olig2 RNAi adenovirus, and the RNAi-negative control group was given the control adenovirus after the completion of the HIBD model. Infarct lesions and their volumes were observed by triphenyltetrazolium chloride (TTC) staining 3 d after the completion of the adenovirus local injection. The condition of the tissue was characterized by hematoxylin-eosin staining 7 d after the model was established, and cell viability was determined by azure methylene blue staining. Subcellular damage was analyzed by transmission electron microscopy. Rotarod analysis was performed to detect moving behavior ability and an MWM assay was conducted to evaluate the memory. RESULTS TTC staining showed a smaller brain injury area in the Olig2-RNAi group than in the RNAi-negative control group. Hematoxylin-eosin staining indicated the presence of severe cell injury in the hippocampal region after HIBD, which improved after Olig2 knockdown. Azure methylene blue staining and electron microscopy results suggested that the cells improved after Olig2 knockdown. The rats stayed longer on the rotating rod, and their latency in the water maze test was gradually shortened relative to that of the rats in the Olig2-RNAi negative control group. CONCLUSION Olig2 knockdown can promote the repair of hypoxic-ischemic brain damage in newborn rats.