慢性脑缺血对大鼠丘脑神经代谢物质的影响

Effect of chronic brain hypoperfusion on the neurometabolites in rat thalamus

目的为探求慢性脑缺血或脑血流灌注不足(CBH)的过程所导致的缺血性脑损伤的病理生理和神经化学机制,运用离体高分辨质子磁共振波谱(1HNMRS)的方法和免疫组织化学技术,对慢性脑缺血所导致大鼠丘脑神经代谢的影响进行研究。方法建立大鼠慢性低灌注性脑缺血的动物模型,观察手术后延迟期大鼠丘脑内的神经代谢物或神经化学物质包括肌酸/磷酸肌酸(Cr)、乳酸(Lac)、N-乙酰-天冬氨酸复合物(NAA)、γ-氨基丁酸(GABA)、谷氨酸(Glu)、谷氨酰胺(Gln)、牛磺酸(Tau)以及肌醇(myo-Ins)浓度的变化。同时采用免疫组织化学的方法,对该大鼠丘脑区域内的胶质纤维酸性蛋白(GFAP)的变化进行观察。结果与对照组相比较,所检测的实验组大鼠丘脑的主要神经化学物质中,Gln和myo-Ins总浓度显著升高(P<0.01),GABA的总浓度显著降低(P<0.05),而NAA、Cr、Lac、Glu和Tau的总浓度变化差异无统计学意义(P>0.05)。同时,免疫组织化学结果显示,与对照组相比较,实验组大鼠丘脑内星形胶质细胞的标志物质GFAP着色光密度与细胞数量均显著增强和增加。结论慢性脑血流灌注不足过程中,大鼠丘脑区域内的一些神经代谢物质仍未能恢复到正常水平,这可能与其导致的慢性神经损伤有关;同时,多种重要的神经代谢物质维持正常水平,可能是神经系统内自我保护机制作用的显示。

Objective To explore the pathophysiological and neurochemical mechanism of brain injury with chronic brain hypoperfusion, ex vivo high resolution 1H NMR spectroscopy and immunohistochemistry were used to investigate the effects induced by chronic cerebral ischemia on rat thalamus. Methods Bilateral common carotid arteries were occluded permanently to produce the experimental animal model of chronic hypoperfusion. The changes of multiple neurochemicals or neurometabolites such as creatine phosphocreatine （Cr）, lactate （Lac）, N-acetyl-aspartate containing compounds （NAA）, gama-aminobutyric acid （GABA）, glutamate （Glu）, glutamine （Gin）, taurine （Tau）, myo-inositol （myo-Ins） in the thalamus of the rats suffered from chronic hypoperfusion were estimated, and immunhistochemistry was used to observe the changes of glial fibrillary acidic protein （GFAP） of this cerebral region simultaneously. Results Compared with the control group, the main neurochemicals in the thalamus of the experimental group showed that the concentrations of Gin and myo-Ins increased significantly （P〈0.01）, of GABA decreased （P〈0.05）, while, the total concentration of Lac, Cr, NAA, Glu and Tau were of the relevant stable, and the immunohistochmical results showed that compared with the control group, the GFAP staining of the thalamus was noticeable deeper, and the number of the GFAP positive cells increased apparently. Conclusion Even in the course of chronic brain hypoperfusion, some neurometabolites could not recovery to the normal level, which may be a factor inducing the chronic nerve injury, meanwhile, most important neurometabolites maintained normally may due to the mechanism of self-protection in the nervous system.