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岩藻聚糖硫酸酯(褐藻糖胶)通过增强细胞外信号调节激酶的激活来抑制乙肝病毒复制。

Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation.

机构信息

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.

Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.

出版信息

Virol J. 2017 Sep 16;14(1):178. doi: 10.1186/s12985-017-0848-8.

Abstract

BACKGROUND

Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not.

METHODS

The HBV-infected mouse model was established by hydrodynamic injection of HBV replicative plasmid, and the mice were treated with saline or fucoidan respectively. Besides, we also tested the inhibitory effect of fucoidan against HBV infection in HBV-transfected cell lines.

RESULTS

The result showed that fucoidan from Fucus vesiculosus decreased serum HBV DNA, HBsAg and HBeAg levels and hepatic HBcAg expression in HBV-infected mice. Moreover, fucoidan treatment also suppressed intracellular HBcAg expression and the secretion of the HBV DNA as well as HBsAg and HBeAg in HBV-expressing cells. Furthermore, we proved that the inhibitory activity by fucoidan was due to the activation of the extracellular signal-regulated kinase (ERK) pathway and the subsequent production of type I interferon. Using specific inhibitor of ERK pathway abrogated the fucoidan-mediated inhibition of HBV replication.

CONCLUSION

This study highlights that fucoidan might be served as an alternative therapeutic approach for the treatment of HBV infection.

摘要

背景

乙型肝炎病毒(HBV)感染是一个严重的公共卫生问题,可导致肝硬化和肝细胞癌。由于目前治疗方法的临床应用有限,因此迫切需要开发新的治疗方法来预防和治疗 HBV 感染。褐藻糖胶是一种从不同种褐藻中提取的天然硫酸化多糖,具有多种生物活性。然而,褐藻糖胶是否影响 HBV 复制尚不清楚。

方法

通过 HBV 复制质粒的流体动力学注射建立 HBV 感染的小鼠模型,分别用生理盐水或褐藻糖胶处理小鼠。此外,我们还测试了褐藻糖胶对 HBV 转染细胞系中 HBV 感染的抑制作用。

结果

结果表明,来自泡叶藻的褐藻糖胶降低了 HBV 感染小鼠的血清 HBV DNA、HBsAg 和 HBeAg 水平以及肝内 HBcAg 表达。此外,褐藻糖胶处理还抑制了 HBV 表达细胞内 HBcAg 表达以及 HBV DNA、HBsAg 和 HBeAg 的分泌。此外,我们证明褐藻糖胶的抑制活性是由于细胞外信号调节激酶(ERK)途径的激活以及随后产生的 I 型干扰素。使用 ERK 途径的特异性抑制剂可消除褐藻糖胶介导的 HBV 复制抑制作用。

结论

本研究强调褐藻糖胶可能成为治疗 HBV 感染的一种替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/5603053/a514aa7ea41a/12985_2017_848_Fig1_HTML.jpg

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