HIV-1gp120通过影响NR2B、PSD-95表达损伤神经元

HIV-1gp120 injures neurons by alteration of neuronal expressions of NR2B and PSD-95

目的研究HIV-1病毒的表面包膜糖蛋白gp120对大鼠皮质神经元的毒性机制。方法实验用SD胎鼠来源的原代培养的皮层神经元,用免疫细胞化学染色和Western blot法检测gp120对含2B亚基的NMDA受体(NR2B)和突触后致密蛋白95(PSD-95)表达的影响,用MTT法检测gp120对神经元的毒性。结果 gp120对神经元有剂量依赖性的毒性作用,其毒性能被NR2B特异拮抗剂美金刚阻断。gp120能明显增加大鼠皮层神经元总NR2B的表达,而降低PSD-95的表达量。结论 gp120可通过使神经元NR2B表达增加及PSD-95的表达减少来损伤神经元,NR2B特异受体拮抗剂能阻止gp120诱导的神经元损伤。

Objective To investigate the mechanisms underlying HIV-1 envelope glycoprotein 120 （gpl20）-associated neurotoxicity on rat cortical neuronal cultures. Methods Experiments were carried out on primary cortical neuronal cultures prepared from fetal Sprague-Dawley fetal rats. Immunocytochemistry and Western blot techniques were employed to examine the changes of the expressions of N-methyI-D-asparate receptors 2B （NR2B） and postsynaptic density 95 （PSD-95） in cultured neurons in the presence and absence of gp120 in the culture media. Gp120-induced neurotoxicity was determined by MTT assay. Results Ml-r assay showed gpl20 produced dose-dependent neuronal injury when added to the culture media and the gpl20-induced neuronal injury was blocked by memantine, a specific NR2B receptor antagonist. Further studies revealed that gpl20 induced neuronal injury by up-regulation of NR2B and down-regulation of PSD-95 expressions in rat cortical neurons. Conclusion These results demonstrated that gp120 injures neurons via an increase of NP,2B and a decrease of PSD-95 expressions. The gp120-induced neuronal injury can be blocked by a specific NR2B receptor antagonist, suggesting NR2B may function as a potential target for the development of therapeutic strategies.