Zhang Jie, Fang Xin, Zhou Yiyi, Deng Xia, Lu Yi, Li Jiao, Li Shujuan, Wang Bo, Xu Renshi
Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1471-8. doi: 10.1016/j.jstrokecerebrovasdis.2015.02.008. Epub 2015 Apr 28.
The pathogenesis of cerebral ischemia-reperfusion injury (CIRI) is not completely clear and therapies are limited now. Therefore, our study aimed to investigate the possible pathogenesis and preventive approach of CIRI through analyzing changes of aspartate (Asp), glutamate (Glu), mitochondrial calcium (MCa), calmodulin (CaM), and malondialdehyde (MDA) contents and ultramicropathology in hippocampus and cerebral cortex of ischemic susceptible injured regions and the effect of monosialotetrahexosylganglioside (GM1) in the rat model of CIRI.
Contents of Asp, Glu, MCa, CaM, and MDA in hippocampus and cerebral cortex tissues were measured by a high-performance liquid chromatography, atomic absorption spectrophotometer, and ordinary spectrophotometer, respectively, changes of ultramicrostructure in neurons of the hippocampus CA1 region and frontal cerebral cortex were observed by a transmission electron microscope.
Contents of Asp and Glu in hippocampus and cerebral cortex tissues of CIRI groups significantly decreased and contents of MCa, CaM, and MDA significantly increased than those in control groups, and the ultramicrostructure in neurons of the hippocampus CA1 region and frontal cerebral cortex revealed a significant damaged change, and GM1 significantly ameliorated changes of Asp, Glu, MCa, CaM, and MDA contents in hippocampus and ultrastructural changes in neurons of the hippocampus CA1 region and frontal cerebral cortex.
Our findings further support that the abnormal release and/or reuptake of excitatory amino acid neurotransmitters, the disordered calcium homeostasis and the excessive production and/or reduced elimination of reactive oxygen species contribute to the pathogenesis of CIRI, and GM1 can partially prevent these pathogenesises to exert the protective effect on CIRI.
脑缺血再灌注损伤（CIRI）的发病机制尚不完全清楚，目前治疗方法有限。因此，我们的研究旨在通过分析缺血易感损伤区域海马和大脑皮质中天冬氨酸（Asp）、谷氨酸（Glu）、线粒体钙（MCa）、钙调蛋白（CaM）和丙二醛（MDA）含量的变化以及超微病理学，探讨CIRI可能的发病机制和预防方法，以及单唾液酸四己糖神经节苷脂（GM1）在CIRI大鼠模型中的作用。
分别采用高效液相色谱法、原子吸收分光光度计和普通分光光度计测定海马和大脑皮质组织中Asp、Glu、MCa、CaM和MDA的含量，用透射电子显微镜观察海马CA1区和额叶大脑皮质神经元超微结构的变化。
与对照组相比，CIRI组海马和大脑皮质组织中Asp和Glu含量显著降低，MCa、CaM和MDA含量显著升高，海马CA1区和额叶大脑皮质神经元超微结构显示出明显的损伤变化，GM1显著改善了海马中Asp、Glu、MCa、CaM和MDA含量的变化以及海马CA1区和额叶大脑皮质神经元的超微结构变化。
我们的研究结果进一步支持兴奋性氨基酸神经递质的异常释放和/或重摄取、钙稳态紊乱以及活性氧的过度产生和/或清除减少是CIRI发病机制的一部分，GM1可以部分预防这些发病机制，从而对CIRI发挥保护作用。
