脑出血后脑组织中兴奋性氨基酸与脑损伤的关系

Pathological Research on the Mechanism of the Brain Damage and Its Relationship with the Expression of Excitatory Amino Acids after Intracerebral Hemorrhage

目的通过收集临床手术治疗的高血压脑出血(HICH)患者的脑组织标本,研究脑出血后血肿周围脑组织细胞凋亡的病理变化及其与兴奋性氨基酸(EAAs)的关系。方法临床脑组织标本均于开颅手术中取材,术中获取不同时段血肿灶周围脑组织标本作为实验组,手术入路中远隔血肿部位脑组织标本作为对照组。根据发病至手术时间将实验组标本分为:超早期组(<8h);早期组(8～24h);延期组(>24h)。所有标本均行TUNEL染色观察凋亡细胞数量;应用高效液相色谱仪(HPLC)检测谷氨酸(Glu)和天门冬氨酸(Asp)含量。结果共收集临床脑组织标本19例:超早期组6例;早期组8例;延期组5例。对照组5例。对照组中各视野未见TUNEL阳性细胞,而病例组3个不同手术时段的凋亡阳性细胞数均高于对照组(P<0.01)。超早期组Asp、Glu含量明显高于对照组(P<0.01),随后均逐渐下降,Asp于早期组即接近对照组(P>0.05),而Glu下降较为缓慢,在早期组仍高于对照组间(P<0.01)。结论凋亡机制参与了脑出血后血肿周围早期神经细胞损伤的过程。Glu、Asp在脑出血后早期明显升高,增高的EAAs可能参与了诱导细胞凋亡发生。

Objective To investigate the apoptosis expression in perihematoma region by collecting clinical pathological specimens from the operative patients with hypertensive intracerebral hemorrhage(HICH),and to explore its relationship with excitatory amino acids(EAAs) contents.Methods Total 19 samples were obtained from the perihematoma region of HICH patients and divided into 3 groups according to the time from onset to operation:super-early phase(<8h),early phase(8-24h) and delayed phase(>24h).Five samples were obtained from distant regions as the normal control group.Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) was used to detect apoptosis,and high performance liquid chromatography(HPLC) was used to determine the EAAs contents.Results TUNEL positive cells were found in the perihematoma region of HICH patents and increased to the peak during the time of 8-24 hours after onset.The expression of glutamic acid(Glu) and aspartic acid(Asp) increased significantly in super-early phase(<8h) compared with the control group(P<0.01).Then both of them began to decline and Asp declined faster than Glu,and in early phase(8-24h) there was not significant difference of Asp compared with the control group(P>0.05).However the level of Glu remained significantly higher than that in control group in early phase(P<0.01).Conclusion Apoptosis as a pattern of cell death takes part in the neuronal injury after intracerebral hemorrhage(ICH).High levels of Glu and Asp during the early time of ICH may induce apoptosis through different ways.