血管性认知障碍小鼠脑内少突胶质细胞再生分化障碍特点研究

摘要/Abstract

摘要：

目的观察血管性认知障碍小鼠模型中，缺血性炎性损伤对室管膜下区及海马齿状回少突胶质细胞再生分化的影响，为血管性认知障碍的缺血性炎症机制提出新的损伤途径。方法成年雄性CD1小鼠随机分为模型组和假手术组，每组24只，模型组采用双侧颈动脉反复缺血再灌注法制备血管性认知障碍小鼠模型。造模后4～6 d连续腹腔注射5 -溴脱氧尿嘧啶核苷（bromodeoxyuridine，BrdU）（150 mg/kg）标记新生细胞，分别于术后14 d和28 d每组随机取一半小鼠脑组织进行脑切片免疫组化、免疫荧光双标共聚焦检测，标记脑组织室管膜下区和海马区的少突胶质细胞、星形胶质细胞及神经元，观察新生少突胶质细胞增殖及分化情况，并观察星形胶质细胞的增生活化情况。结果造模后14 d和28 d室管膜下区新生细胞（BrdU阳性细胞）在模型组较假手术组明显增加（P均＜0.001)，造模28 d模型组新生神经元（BrdU/NeuN阳性细胞）较假手术组显著增加（P＜0.001)。与假手术组相比较，术后28 d模型组海马齿状回少突胶质细胞祖细胞显著增多（P＜0.001）；少突胶质细胞前体细胞显著减少（P =0.006）。造模后28 d模型组海马齿状回新生星形胶质细胞（BrdU/GFAP阳性细胞）较假手术组显著增加（P =0.015）。结论血管性认知障碍小鼠内源性新生细胞增殖区室管膜下区与海马齿状回区均存在新生细胞反应性增生的情况。新生细胞区分化的主要细胞为星形胶质细胞，而少突胶质细胞分化障碍，可能是血管性认知障碍患者影像学常见皮层下白质病变的重要原因。

文章导读： 血管性认知障碍动物模型中观察到缺血性炎性损伤对室管膜下区及海马齿状回少突胶质细胞再生分化的影响。

关键词: 血管性认知障碍; 神经再生; 少突胶质细胞; 星形胶质细胞

Abstract:

Objective To observe the neurogenesis in subventricular zone and regeneration of oligodendrocyte in dentate gyrus of hippocampus in a mice model of vascular cognitive impairment(VCI). Methods Adult CD1 males mice were randomly divided into model group and sham group with 24 mice in each group. Mice in model group were subjected to repeated bilateral carotid artery occlusion and reperfusion to establish the animal model of VCI. Mice in sham group were conducted the same surgery expect occluding carotid artery. All mice were administrated 5-bromine deoxidization uracil nucleoside (150 mg/kg, intraperitoneal injection, qd) from the post operation day(POD) 4 to 6. On POD 14 and 28, 12 mice from each group were deeply anesthetized and transcardially perfused with phosphate buffered saline(PBS) respectively. Brain frozen sections were prepared for immunohistochemical and immunofluorescence double staining to observe the new cell proliferation and neuronal regeneration in subventricular zone on POD 14 and POD 28, and the regeneration of oligodendrocytes and expression of newborn astrocytes in dentate gyrus on POD 28. Results On POD 14 and 28, there were both significant differences in the number of newborn cells in subventricular zone between two groups (P <0.001). Compared with sham group, on POD 28, thenumber of newborn neuron in subventricular zone of mice from model group increased significantly (P <0.001). Compared with sham group, the number of oligodendrocytes progenitor cells in dentate gyrus was significantly increased in model group on POD 28 (P <0.001), with pre-oligodendrocytes reduced (P =0.006) and mature oligodendrocytes decreased but with no statistically significant difference (P =0.161). Compared with sham group, the number of new born astrocytein the dentate gyrus increased significantly in model group (P =0.015). Conclusion There was endogenous neurogenesis in VCI mice, but the regeneration of mature oligodendrocytes in dentate gyrus was dysfunction, which might be the cause of white matter hyperintensities displayed in magnetic resonance imaging(MRI) of patients with VCI.

Key words: Vascular cognitive impairment; Neurogenesis; Oligodendrocyte; Astrocyte

李海龙，郑惠文，刘敏，黎佳思，王云霞，赵善民，毕晓莹. 血管性认知障碍小鼠脑内少突胶质细胞再生分化障碍特点研究[J]. 中国卒中杂志, 2015, 10(11): 935-940.

LI Hai-Long, ZHENG Hui-Wen, LIU Min, et al.. Characteristics of Oligodendrocytes Regeneration Dysfunction in Vascular CognitiveImpairment Mice[J]. Chinese Journal of Stroke, 2015, 10(11): 935-940.

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