血小板膜与脑细胞线粒体和突触体外周型苯二氮卓受体的相关性及生物学意义

Correlations between peripheral benzodiazepine receptors in mitochondria,synaptosomes in brain cells and platelet membrane and biological significance

目的:探讨衰老过程中脑细胞线粒体和突触体外周型苯二氮卓受体(PBRs)的动态变化以及与外周血血小板膜PBRs相关性的生物学意义。方法:实验动物分为3月龄、12月龄和24月龄3组。动物断头取血后,迅速取脑。采用梯度离心技术提取大脑皮质线粒体和海马突触体,低渗溶血法制备外周血血小板膜。应用放射配基[3H]PK11195结合实验测定PBR结合活力。结果:3组比较,大脑皮质线粒体(F=194.6)、海马突触体(F=94.2)、外周血血小板膜(F=162.2)[3H]PK11195结合活性差异均有显著性(P<0.001)。随着鼠龄增加,上述指标显著下降。外周血血小板膜[3H]PK11195结合活性与大脑皮质线粒体(r=0.894)、海马突触体(r=0.893)[3H]PK11195结合活性比较差异均具有显著性(P<0.001)。结论:大脑皮质线粒体、海马突触体PBRs水平呈增龄下降改变,外周血血小板膜[3H]PK11195结合活性能够反映脑组织该指标的变化。

Objective To investigate correlations between peripheral benzodiazepine receptors （PBRs） in mitochondria and synaptosomes in the brain and platelet membrane of rats during aging and to explore the significance of the relationships. Methods Sprague-Dawley rats of both sexes were divided into 3-, 12- and 24-month groups. All animals were sacrificed by decapitation and the brains were immediately removed. Mitochondrial components from dissected cerebral cortex and synaptosomal fractions from dissected hippocampus were isolated by gradient centrifugation. The membrane of platelets from venous blood was prepared by the method of hypotonic haemolysis. The specific binding assay of the radioactive PBRs antagonist [3^ H] PK11195 to membrane was performed. Results A significant difference about[3^ H] PK11195 binding activity of mitochondria was observed among three groups （F= 194. 6, P〈0. 001）, while the same change was noted for synaptosomes （F= 94. 2, P〈0. 001） and for platelet membrane （F=162.2, P〈0. 001）. An age-related decrease was found for the three indexes above. A positive relationship about [3^ H] PK11195 binding activity （P〈0. 001） was found between platelet membrane and cortex mitochondria （r = 0. 894） as well as hippocampus synaptosomes （r = 0. 893）.Conclusion The levels of PBRs decrease in cortex mitochondria and hippocampus synaptosomes with aging in rats.[3^ H] PK11195 binding activity of platelet membrane might reflect the changes of PBRs in the brain tissue.