肽核酸在鸭乙型肝炎病毒感染模型中的抗病毒作用。
Antiviral effects of PNA in duck hepatitis B virus infection model.
作者信息
Chen Zong-Yan, Cheng An-Chun, Wang Ming-Shu, Xu Da-Wei, Zeng Wen, Li Zhan
机构信息
Avian Disease Research Center, College of Animal Science and Veterinary Medicine, Sichuan Agricultural University, Ya-an 625014, China.
出版信息
Acta Pharmacol Sin. 2007 Oct;28(10):1652-8. doi: 10.1111/j.1745-7254.2007.00641.x.
AIM
To study the efficacy of antiviral treatment with PNA for the duck model of HBV (DHBV)-infected ducks. PNA is a 2-amine-9-(2,3-dideoxy-2,3-dihydro-beta-D-arabinofuranosyl)-6-methoxy-9H-purine.
METHODS
The Sichuan Mallard ducklings in the hepatitis B virus model were treated with PNA, a new antiviral agent. DHBV DNA from the blood serum and liver tissues were measured at 0, 5, and 10 d during the treatment and at 3 d withdrawal by real-time PCR. The duck hepatitis B surface antigen (DHBsAg) in the liver cells was observed by Immunohistochemistry (IHC). Pathological changes in the liver tissues were also observed. Control group I was administered with distilled water and control group II was administered with 3-thiacytidine. Treatment group I was administered with PNA at a dose of 40 mg/kg and treatment group II was administered perorally (po) with PNA at a dose of 80 mg/kg. Treatment group III was administered with PNA at a dose of 20 mg/kg and treatment group IV was intravenously administered with PNA at a dose of 40 mg/kg. Each group contained 15 ducklings.
RESULTS
PNA can significantly lower the DHBV replication levels in serum and liver. Compared with control group II, there were no significant differences in inhibiting efficacy in treatment groups I and III (P>0.05) and there were significant differences in inhibiting efficacy in treatment groups II and IV (P<0.05). Interestingly, significant differences were observed at 3 d withdrawal. The DHBV replication levels in each group slightly increased at 3 d withdrawal, but rebounded slightly in the PNA treatment groups than in control group II (P<0.05). The DHBV replication levels in the treatment groups were lower than in control group I. The DHBV replication levels in sera had a positive relationship with that in the liver, but the DHBV replication levels in the liver was lower than that in sera. Pathological changes in the treatment groups were obviously improved and the changes were associated with liver viral DNA levels.
CONCLUSION
The results demonstrate that PNA is a strong inhibitor of DHBV replication in the DHBV-infected duck model.
目的
研究嘌呤核酸类似物（PNA）对乙型肝炎病毒感染鸭（DHBV）模型鸭的抗病毒治疗效果。PNA是一种2-氨基-9-(2,3-二脱氧-2,3-二氢-β-D-阿拉伯呋喃糖基)-6-甲氧基-9H-嘌呤。
方法
用新型抗病毒药物PNA对乙型肝炎病毒模型中的四川绿头鸭雏鸭进行治疗。在治疗的第0、5和10天以及停药后第3天，通过实时聚合酶链反应（PCR）检测血清和肝组织中的DHBV DNA。通过免疫组织化学（IHC）观察肝细胞中的鸭乙型肝炎表面抗原（DHBsAg）。还观察了肝组织的病理变化。对照组I给予蒸馏水，对照组II给予3-硫代胞苷。治疗组I给予40mg/kg剂量的PNA，治疗组II口服80mg/kg剂量的PNA。治疗组III给予20mg/kg剂量的PNA，治疗组IV静脉注射40mg/kg剂量的PNA。每组包含15只雏鸭。
结果
PNA可显著降低血清和肝脏中DHBV的复制水平。与对照组II相比，治疗组I和III的抑制效果无显著差异（P>0.05），治疗组II和IV的抑制效果有显著差异（P<0.05）。有趣的是，在停药后第3天观察到显著差异。每组的DHBV复制水平在停药后第3天略有升高，但PNA治疗组比对照组II略有反弹（P<0.05）。治疗组的DHBV复制水平低于对照组I。血清中的DHBV复制水平与肝脏中的呈正相关，但肝脏中的DHBV复制水平低于血清中的。治疗组的病理变化明显改善，且这些变化与肝脏病毒DNA水平相关。
结论
结果表明，PNA是DHBV感染鸭模型中DHBV复制的强效抑制剂。
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