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磷酸化和硫酸化黄芪多糖抗鸭甲型肝炎病毒活性的比较。

Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides.

作者信息

Wang Yixuan, Chen Yun, Du Hongxu, Yang Jingjing, Ming Ke, Song Meiyun, Liu Jiaguo

机构信息

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P R China.

出版信息

Exp Biol Med (Maywood). 2017 Feb;242(3):344-353. doi: 10.1177/1535370216672750. Epub 2016 Oct 4.

Abstract

Duck hepatitis A virus (DHAV) (Picornaviridae) causes an infectious disease in ducks which results in severe losses in duck industry. However, the proper antiviral supportive drugs for this disease have not been discovered. Polysaccharide is the main ingredient of Astragalus that has been demonstrated to directly and indirectly inhibit RNA of viruses replication. In this study, the antiviral activities of Astragalus polysaccharide (APS) and its derivatives against DHAV were evaluated and compared. APS was modified via the sodium trimetaphosphate and sodium tripolyphosphate (STMP-STPP) method and chlorosulfonic acid-pyridine method to obtain its phosphate (pAPS) and sulfate (sAPS), respectively. The infrared structures of APS, pAPS, and sAPS were analyzed with the potassium bromide disc method. Additionally, the antiviral activities were evaluated with the MTT ((4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method in vitro and the artificial inoculation method in vivo. The clinical therapy effects were evaluated by mortality rate, liver function-related biochemical indicators, and visual changes in pathological anatomy. The anti-DHAV proliferation effects of APS, pAPS, and sAPS on the viral multiplication process in cell and blood were observed with the reverse transcription-polymerase chain reaction method. The results revealed that pAPS inhibited DHAV proliferation more efficiently in the entire process of viral multiplication than APS and sAPS. Moreover, only pAPS significantly improved the survival rate to 33.5% and reduced the DHAV particle titer in the blood as well as liver lesions in clinical trials. The results indicated that pAPS exhibited greater anti-DHAV activity than APS and sAPS both in vitro and in vivo.

摘要

鸭甲型肝炎病毒(DHAV)(微小核糖核酸病毒科)可在鸭群中引发一种传染病,给养鸭业造成严重损失。然而,针对该疾病的合适抗病毒支持性药物尚未被发现。多糖是黄芪的主要成分,已证明其能直接或间接抑制病毒RNA复制。在本研究中,对黄芪多糖(APS)及其衍生物抗DHAV的活性进行了评估和比较。通过偏磷酸钠和三聚磷酸钠(STMP - STPP)法以及氯磺酸 - 吡啶法对APS进行修饰,分别得到其磷酸盐(pAPS)和硫酸盐(sAPS)。采用溴化钾压片法分析了APS、pAPS和sAPS的红外结构。此外,通过MTT((4,5 - 二甲基 - 2 - 噻唑基)- 2,5 - 二苯基 - 2 - H - 四氮唑溴盐)法在体外和人工接种法在体内评估抗病毒活性。通过死亡率、肝功能相关生化指标以及病理解剖的外观变化评估临床治疗效果。采用逆转录 - 聚合酶链反应法观察APS、pAPS和sAPS对细胞和血液中病毒增殖过程的抗DHAV增殖作用。结果显示,在病毒增殖的整个过程中,pAPS比APS和sAPS更有效地抑制DHAV增殖。此外,在临床试验中,只有pAPS显著提高了存活率至33.5%,并降低了血液中的DHAV颗粒滴度以及肝脏病变。结果表明,pAPS在体外和体内均表现出比APS和sAPS更强的抗DHAV活性。

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