人类免疫缺陷病毒蛋白HIV gp120对培养的大鼠背根神经节神经元的神经毒性作用(英文)

NEUROTOXIC EFFECT OF HIV gp120 ON CULTURED RAT DORSAL ROOT GANGLION NEURONS

为探讨人类免疫缺陷病毒(HIV)gp120对体外培养的大鼠背根神经节(DRG)神经元的神经毒性作用,我们建立了胎鼠DRG分散培养和器官型培养的模型。以上分散培养和器官型培养的DRG,经不同浓度(250pmol/L,1nmol/L)的HIVgp120处理(2次/7d)。分散培养的DRG细胞行微管相关蛋白2(MAP2)免疫荧光染色,然后利用荧光显微镜观察神经元胞体和突起的变化情况。器官型培养的DRG在电子显微镜下观察其超微结构的改变。经HIVgp120处理的神经元突起的数目和长度的变化,HIVgp120处理组与对照组相比有显著性意义(P<0.001),而神经元的直径则没有变化(P>0.05)。应用以上不同浓度的HIVgp120处理后,神经元的超微结构出现明显改变,线粒体嵴减少或消失,微管和神经丝之间出现了大量的高电子密度颗粒。以上结果表明,HIVgp120对培养的DRG神经元具有直接的神经毒性作用,其中以线粒体的改变较为敏感。

To investigate the neurotoxic effect of human immunodeficiency virus （HIV） gp120 on cultured dorsal root ganglion （DRG） neurons in vitro, dissociated and organotypic mouse embryo＇s DRG cell culture models were established. Both dissociated and organotypic DRG cultures were treated with HIV gp120 in different concentration （250 pmol/L and 1 nmol/L, respectively, 2 times/7 days）. For dissociated DRG cultural cells, microtubule-associated protein 2 （ MAP2 ） immunofluorescent labeling was processed for observing the changes of neuronal cell body and neurites. The change of the uhrastructure in the organotypic cultured DRG was observed by electron microscopy. The difference of the number and length of neurites between the control group and HIV gp120 treated groups were significant （ P 〈 0. 001 ）, whereas there was no significant difference in the diameter of neurons between them （ P 〉0.05 ）. The ultrastructural changes included the decrease or loss of cristae in mitocbondria and accumulation of many high densed particles between the microtubules and the neurofilaments by using both the concentrations of HIV gp120 treatment. The present results indicate that HIV gp120 had a directly neurotoxic effect on the cultured DRG neurons, especially more sensitive to mitocbondria.