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杨晓枫,张丽颖,罗 婧,李明月,李莉莉,胡昔权.预运动训练对高血压大鼠急性脑梗死后梗死周围区神经元存活及星形胶质细胞的影响[J].中国康复医学杂志,2021,(7):767~773
预运动训练对高血压大鼠急性脑梗死后梗死周围区神经元存活及星形胶质细胞的影响    点此下载全文
杨晓枫  张丽颖  罗 婧  李明月  李莉莉  胡昔权
中山大学附属第三医院康复医学科,广州,510630
基金项目:广州市科技计划项目(201803010119);国家自然科学基金面上项目(81672261)
DOI:10.3969/j.issn.1001-1242.2021.07.001
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摘要:
      摘要 目的:探讨星形胶质细胞表达的胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)和脂钙蛋白2(lipocalin 2,LCN2)在预运动训练对高血压大鼠急性脑梗死后神经元存活中的作用。 方法:采用自发性高血压大鼠(spontaneously hypertensive rats,SHR)共45只,随机分为假手术组(S,n=5)、对照组(C,n=20)及预运动训练组(PE,n=20)。预运动训练组给予1个月中等强度的跑笼训练。采用线栓法建立大脑中动脉闭塞再灌注模型。术后24h,采用改良神经损伤程度评分(modified neurological severity scores,mNSS)对各组大鼠进行神经功能评估后取材,2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色评估梗死体积;免疫荧光法观察梗死周围区神经元数量,同时比较星形胶质细胞标志物(glial fibrillary acidic protein,GFAP)和神经元标志物(neuronal nuclear antigen,NeuN)分别与IGF-1、LCN2这两种因子共定位表达的情况,并采用相关性分析探讨IGF-1、LCN2与神经元存活数量的关系。 结果:造模术后24h,PE组mNSS评分、梗死体积优于C组,且存活的神经元数量更多,差异均有显著性。PE组大鼠梗死周围区GFAP+/IGF-1+细胞数多于C组(P<0.05),GFAP+/LCN2+细胞数明显少于C组(P<0.001)。相关性分析提示,IGF-1、LCN2阳性细胞数与存活神经元数量分别成正(r=0.54,P=0.008)、负(r=-0.59,P=0.004)相关。 结论:预运动训练能够减轻高血压大鼠急性脑梗死后神经功能损伤、减小梗死体积、促进神经元存活,其机制可能与预运动训练促进梗死周围区星形胶质细胞IGF-1表达、抑制LCN2表达有关。
关键词:预运动训练  脑梗死  星形胶质细胞  胰岛素样生长因子1  脂钙蛋白2
Effects of preconditioning exercise on neuronal survival and roles of astrocytes in the peri-infarct area of spontaneously hypertensive rats with acute cerebral ischemia    Download Fulltext
The Third Hospital Affiliated to Sun Yat-sen University, Guangzhou, 510630
Fund Project:
Abstract:
      Abstract Objective: To investigate the effect of two astrocytes’ secretory factors, insulin like growth factors-1 (IGF-1) and lipocalin 2 (LCN2), on neuronal survival in the peri-infarct area after acute cerebral infarction in spontaneously hypertensive rats (SHR) with preconditioning exercise. Method: Forty-five adult SHR were randomly divided into three groups: sham group (S, n=5), control group (C, n=20), and preconditioning exercise group (PE, n=20). The preconditioning exercise group took moderate intensity running exercise daily for one month. 24 hours after being performed with transient middle cerebral artery occlusion (tMCAO), rats were sacrificed after evaluating the neurological function with modified neurological severity scores (mNSS). TTC staining was performed to evaluate the infarct volume. And immunofluorescence staining was employed to calculate neuron, and colocalization expression of astrocyte marker GFAP and neuron marker NeuN with two secretory factors, IGF-1 and LCN2, respectively. Correlation analysis was applied to investigate the effects of IGF-1 and LCN2 on neuronal survival. Result: The mNSS scores, infarct volume and the number of survival neurons in the PE group were much better than the C group at 24 hours after tMCAO, all the differences were significant. Compared with the C group, the number of GFAP+/IGF-1+ double positive cells in the PE group was higher (P<0.05), while the number of GFAP+/LCN2+ was obvious lower (P<0.001). Correlation analysis indicated that the number of IGF-1 positive cells was positively correlated with the number of survival neurons (r=0.54, P=0.008), while LCN2 was negatively correlated (r=-0.59,P=0.004). Conclusion: Preconditioning exercise can reduce neurological function injury and infarction volume, promote neuronal survival in SHR with acute cerebral ischemia, whose mechanism may be related to its up-regulation of IGF-1 expression and down-regulation of LCN2 from astrocytes in the peri-infarct region.
Keywords:preconditioning exercise  cerebral infarction  astrocyte  insulin-like growth factor-1  lipocalin 2
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