Li Yuan, Zhang Ting, Douglas Steven D, Lai Jian-Ping, Xiao Wei-Dong, Pleasure David E, Ho Wen-Zhe
Division of Immunologic and Infectious Diseases, Department of Pediatrics, Stokes Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.
Am J Pathol. 2003 Sep;163(3):1167-75. doi: 10.1016/S0002-9440(10)63476-1.
Little information is available regarding whether substance abuse enhances hepatitis C virus (HCV) replication and promotes HCV disease progression. We investigated whether morphine alters HCV mRNA expression in HCV replicon-containing liver cells. Morphine significantly increased HCV mRNA expression, an effect which could be abolished by either of the opioid receptor antagonists, naltrexone or beta-funaltrexamine. Investigation of the mechanism responsible for this enhancement of HCV replicon expression demonstrated that morphine activated NF-kappaB promoter and that caffeic acid phenethyl ester, a specific inhibitor of the activation of NF-kappaB, blocked morphine-activated HCV RNA expression. In addition, morphine compromised the anti-HCV effect of interferon alpha (IFN-alpha). Our in vitro data indicate that morphine may play an important role as a positive regulator of HCV replication in human hepatic cells and may compromise IFN-alpha therapy.
关于药物滥用是否会增强丙型肝炎病毒（HCV）复制并促进HCV疾病进展，目前可用信息较少。我们研究了吗啡是否会改变含HCV复制子的肝细胞中HCV mRNA的表达。吗啡显著增加了HCV mRNA的表达，而阿片受体拮抗剂纳曲酮或β-氟纳曲胺中的任何一种都可以消除这种作用。对负责增强HCV复制子表达的机制进行研究表明，吗啡激活了NF-κB启动子，而咖啡酸苯乙酯作为NF-κB激活的特异性抑制剂，可阻断吗啡激活的HCV RNA表达。此外，吗啡损害了干扰素α（IFN-α）的抗HCV作用。我们的体外数据表明，吗啡可能作为人类肝细胞中HCV复制的正调节剂发挥重要作用，并可能损害IFN-α治疗。
