HIV-1包膜蛋白gp120在神经元损伤诱发认知障碍中的作用

目的探索HIV-1包膜蛋白gp120在神经元损伤引起认知障碍中的作用。方法免疫印迹和免疫荧光检测gp120处理后的小胶质细胞活化、炎症因子表达和神经元损伤情况;免疫组化分析gp120转基因小鼠的神经元损伤情况;行为学分析转基因小鼠的神经认知状况。结果体内和体外试验结果表明HIV-1 gp120可显著诱导caspase-1与IL-1β表达,并间接引起神经元突触变短和神经元损伤(P<0.05);与野生型小鼠相比,gp120转基因小鼠出现明显的皮层和海马回小胶质细胞激活、神经元丢失与树突损伤以及神经认知紊乱现象。结论HIV-1 gp120可能通过激活小胶质细胞炎症因子释放导致神经元损伤并可能与神经认知障碍发生相关。

Role of HIV-1 envelope protein gp120 in neuronal injury-induced cognitive impairment

Objective To investigate the role of HIV-1 envelope protein gp120 in cognitive impairment induced by neuronal damage.Methods Western blot and immunofluorescence assay were used to detect microglia activation,inflammatory factor expression and neuronal damage after gp120 treatment.Neuronal damage and neurocognitive performance in gp120-transgenic mice were evaluated using immunohistochemical staining and behavioral analysis,respectively.Results In vivo and in vitro experiments showed that HIV-1 gp120 significantly induced the expression of caspase-1 and IL-1β,and indirectly caused neuronal synaptic shortening and neuronal damage(P<0.05).Compared with wild-type mice,gp120-transgenic mice showed significant cortical and hippocampal glial activation,neuronal loss,dendritic damage and neurocognitive disorders.Conclusions HIV-1 gp120 might cause neuronal damage through activating the release of inflammatory factor by microglia and involve in neurocognitive impairment.