巨噬细胞外泌体抑制HBV DNA复制

目的探讨巨噬细胞(macrophage,M?)外泌体抑制HBV DNA复制的机制及与慢性乙型肝炎(chronic viral hepatitis B,CHB)肝损伤的相关性。方法体外分离鉴定M?外泌体,并将其与Hep G2.2.15细胞共培养,利用实时定量PCR检测共培养后HBV DNA复制的变化,分别分析M?及其上清外泌体中微小RNA(micro RNA,mi RNA)-638的表达;同时入组CHB免疫活化(immune activation,IA)期、低(非)复制(inactive carrier,IC)期患者,并以同期健康者作为对照组,通过实时定量PCR检测血清外泌体中mi RNA-638的表达,并与肝损伤、HBV DNA载量进行相关性分析。结果 M?外泌体可以抑制HBV DNA复制;M?及其上清外泌体中mi RNA-638高表达;CHB患者IA期mi RNA-638的表达水平低于IC期;CHB患者血清外泌体中mi RNA-638的表达水平与ALT、AST和HBV DNA水平呈负相关。结论 M?外泌体可以抑制HBV DNA复制,外泌体中mi RNA-638的表达水平与肝脏炎性损伤和病毒复制密切相关,M?外泌体相关mi RNA可能是潜在的抑制HBV复制、减轻肝脏炎症的靶点。

Macrophage-derived exosomes inhibit HBV DNA replication

Objective To investigate the mechanism of macrophage-derived exosomes on inhibiting HBV replication and analyze its relationship with liver damage in chronic hepatitis B (CHB) patients. Methods Macrophage-derived exosomes were isolated in vitro and co-cultured with HepG2.2.15 cells. Real-time quantitive PCR was used to detect the change of HBV DNA replication after co-culture, and the expression levels of microRNA-638 (miRNA-638) in the exosomes isolated from macrophages and supernatant were analyzed. In addition, CHB patients at immune activation (IA) and inactive carrier (IC) stage, as well as healthy controls were included in this study. The miRNA-638 expression level in macrophage-derived exosomes was detected with real-time quantitive PCR, and its correlation with liver damage and HBV DNA load was analyzed. Results Exosomes derived from macrophages could inhibit HBV DNA replication, and miRNA-638 expression upregulated in the exosomes isolated from macrophages and supernatant; miRNA-638 expression decreased in the CHB patients at IA stage compared with that at IC stage; miRNA-638 expression was negatively correlated with ALT, AST, and HBV DNA in the serum exosomes of CHB patients. Conclusions Exosomes derived from macrophage may inhibit HBV DNA replication. miRNA-638 expression in exosomes is closely associated with liver inflammation injury and viral replication. Exosomes associated miRNA in macrophages may be a potential target for inhibiting HBV replication and reducing liver inflammation.