甲基苯丙胺对HIV-1感染人巨噬细胞的影响

Methamphetamine enhances human immunodeficiency virus 1 infection in macrophages

目的研究甲基苯丙胺（METH）是否促进HIV-1感染人巨噬细胞及其机制。方法采集健康成人新鲜外周血，分离单核细胞，再经贴壁法培养纯化为巨噬细胞。用METH和／或多巴胺受体D1阻滞剂对巨噬细胞作预处理，加进HIVBal病毒感染细胞，收集细胞，检测细胞中HIVRNA的水平；同时，采用实时荧光定量PCR检测巨噬细胞多巴胺受体D1的表达，探讨METH在HIV-1感染人巨噬细胞中的作用及可能机制。结果METH处理可增强HIVBal在人巨噬细胞中的感染和复制，呈剂量依赖和时间效应关系；机制研究表明METH是通过细胞的多巴胺受体发挥作用，用多巴胺受体D1阻滞剂（SCH23390）可以阻断METH处理导致的人巨噬细胞感染HIVBal的增强。此外，METH处理可以上调细胞多巴胺受体D1的表达，有助于HIV在细胞中的感染和复制。结论METH可能通过诱导巨噬细胞多巴胺受体D1的表达，促进HIV在巨噬细胞中的感染和复制，是HIV感染的协同因子。

Objective To investigate whether methamphetamine （METH） can enhance human immunodefieieney virus 1 （HIV-1） infection in maerophages and the possible mechanism. Methods Pe- ripheral blood samples were collected from eight healthy adult donors. Monoeytes were isolated from blood samples and then cultured in vitro to induce differentiation to maerophages. These macrophages were treated with METH and/or dopamine receptor D1 （ DRD1 ） antagonist, and then infected with HIV Bal strains. The levels of HIV RNA were measured in HIV Bal-infected macrophages by RT-PCR analysis. The real-time RT- PCR was performed for the quantification of cellular DRD1. Results METH promoted HIV replication in macrophages in a dose and time dependent manner. This METH-mediated enhancement of HIV infection and replication in macrophages could be blocked by the DRD1 antagonist （SCH23390）. Moreover, METH could induce the expression of DRD1. Conclusion METH might play a co-factor role in HIV infection in human macrophages by up-regulating the expression of DRD1.