短暂性和永久性脑缺血大鼠对侧小脑代谢变化

Metabolic alterations in the contralateral cerebellum of rats with transient and permanent middle cerebral artery occlusion

目的:应用基于核磁共振氢谱(1H NMR)的代谢组学技术探讨短暂性(tMCAO)和永久性大脑中动脉闭塞(pMCAO)模型大鼠对侧小脑的代谢变化。方法:将大鼠分为对照组(CON组,n=12)、pMCAO组(n=29)和tMCAO组(n=23),行头颅MRI扫描,并选取对侧小脑组织行1H NMR检测,进行模式识别并定量分析代谢物。结果:3组大鼠对侧小脑MRI未见明显异常,但其代谢模式存在显著差异。pMCAO组较CON组对侧小脑丙氨酸(Ala)、乳酸(Lac)含量显著下降,而γ-氨基丁酸(GABA)、谷氨酰胺(Gln)、肌醇(m-Ins)、天冬氨酸(Asp)、肌酐(Cre)含量显著升高(P<0.05);tMCAO组较CON组对侧小脑Ala、Lac含量显著下降,而谷氨酸(Glu)、m-Ins、Asp、Cre含量显著升高(P<0.05);tMCAO组较pMCAO组对侧小脑Gln含量显著下降(P<0.05)。结论:短暂性和永久性脑缺血大鼠对侧小脑代谢均发生显著改变,主要涉及能量代谢、神经递质代谢和胶质细胞活性。不同时长脑缺血对小脑Gln-Glu-GABA循环代谢影响不同。

Objective:To investigate metabolic alterations in contralateral cerebellum of the transient(tMCAO)and permanent middle cerebral artery occlusion(pMCAO)rats by 1H NMR-based metabolomics.Methods:The rats were divided into CON group(n=12),pMCAO group(n=29)and tMCAO group(n=23).Brain MRI scan was performed and the contralateral cerebellum was detected by 1H NMR with pattern recognition and quantitative analysis of metabolites.Results:Although MRI showed no obvious abnormalities,the metabolic patterns of contralateral cerebellum were significantly changed in three groups.Compared with CON group,alanine(Ala)and lactate(Lac)decreased significantly,whileγ-aminobutyric acid(GABA),glutamine(Gln),myo-inositol(m-Ins),aspartate(Asp)and creatine(Cre)increased significantly for contralateral cerebellum in pMCAO group(P<0.05);Ala and Lac decreased significantly,while glutamate(Glu),m-Ins,Asp and Cre increased significantly for contralateral cerebellum in tMCAO group(P<0.05).Gln of contralateral cerebellum decreased significantly in tMCAO group compared with pMCAO group(P<0.05).Conclusion:The metabolism of the contralateral cerebellum was significantly altered in the transient and permanent cerebral ischemia,mainly involving energy metabolism,neurotransmitter metabolism and glial cell activity.Different ischemic time showed variant impact on Gln-Glu-GABA cycle of cerebellum.