Effect of oxymatrine on the replication cycle of hepatitis B virus in vitro

被引:45
作者
Xu, Wen-Sheng [1 ]
Zhao, Ke-Kai [2 ]
Miao, Xiao-Hui [1 ]
Ni, Wu [1 ]
Cai, Xiong [1 ]
Zhang, Rui-Qi [1 ]
Wang, Jun-Xue [1 ]
机构
[1] Second Mil Med Univ, Changzheng Hosp, Dept Infect Dis, Shanghai 200003, Peoples R China
[2] 404 Hosp, Dept Infect Dis, Weihai 264200, Shandong, Peoples R China
关键词
Oxymatrine; Hepatitis B virus; Replication intermediates; Covalently closed circular DNA; Pregenomic RNA; CLOSED CIRCULAR DNA; ADEFOVIR DIPIVOXIL; INTERFERON-ALPHA; NATURAL-HISTORY; DOUBLE-BLIND; VIRAL-DNA; HEPATOCYTES; INHIBITION; EXPRESSION; INFECTION;
D O I
10.3748/wjg.v16.i16.2028
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To determine the antiviral mechanism or target of oxymatrine against hepatitis B virus (HBV). METHODS: HepG2.2.15 cells were incubated with culture medium containing 500 mu g/mL of oxymatnne for 2 and 5 d. The surface antigen of HBV (HBsAg) and e antigen of HBV (HBeAg) in supernatant were determined by ELISA. HBV DNA in supernatant, and intracellular covalently closed circular DNA (cccDNA), relaxed circular DNA (rcDNA) and pregenomic RNA (pgRNA) were quantified by specific real-time polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. RESULTS: Treatment with oxymatrine for 2 d and 5 d reduced the production of HBV by the cell line, as indicated by the decline of HBsAg (22.67%, t = 5.439, P = 0.0322 and 22.39%, t = 5.376, P = 0.0329, respectively), HBeAg (55.34%, t = 9.859, P = 0.0101 and 43.97%, t = 14.080, P = 0.0050) and HBV DNA (40.75%, t = 4.570, P = 0.0447 and 75.32%, t = 14.460, P = 0.0047) in the supernatant. Intracellular cccDNA was also markedly reduced by 63.98% (t = 6.152, P = 0.0254) and 80.83% (t = 10.270, P = 0.0093), and intracellular rcDNA by 34.35% (t = 4.776, P = 0.0413) and 39.24% (t = 10.050, P = 0.0097). In contrast, intracellular pgRNA increased by 6.90-fold (t = 8.941, P = 0.0123) and 3.18-fold (t = 7.432, P = 0.0176) after 500 mu g/mL of oxymatrine treatment for 2 d and 5 d, respectively. CONCLUSION: Oxymatrine may inhibit the replication of HBV by interfering with the process of packaging pgRNA into the nucleocapsid, or inhibiting the activity of the viral DNA polymerase. (C) 2010 Baishideng. All rights reserved.
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页码:2028 / 2037
页数:10
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