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氧化苦参碱在水动力注射乙肝病毒小鼠模型中的T细胞相关免疫调节及抗病毒作用

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model.

作者信息

Sang Xiuxiu, Wang Ruilin, Han Yanzhong, Zhang Cong'en, Shen Honghui, Yang Zhirui, Xiong Yin, Liu Huimin, Liu Shijing, Li Ruisheng, Yang Ruichuang, Wang Jiabo, Wang Xuejun, Bai Zhaofang, Xiao Xiaohe

机构信息

Chengde Medical College, Chengde 067000, China.

China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China.

出版信息

Acta Pharm Sin B. 2017 May;7(3):311-318. doi: 10.1016/j.apsb.2017.02.005. Epub 2017 May 2.

DOI:10.1016/j.apsb.2017.02.005
PMID:28540167
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5430867/
Abstract

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) , limited research has been done with this drug . In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon- (IFN-) in a dose-dependent manner in CD4 T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

摘要

尽管氧化苦参碱(OMT)已被证明可直接抑制乙型肝炎病毒(HBV)的复制,但针对该药物的研究仍较为有限。在本研究中,我们在具有免疫活性的慢性HBV感染小鼠模型中研究了OMT的抗病毒作用。通过尾静脉注射大量DNA溶液实现感染。OMT(2.2、6.7和20mg/kg)每日腹腔注射给药,持续6周。通过检测HBV DNA、乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)和乙型肝炎核心抗原(HBcAg)的水平来评估OMT的疗效。通过血清ELISA和流式细胞术评估OMT的免疫调节活性。结果显示,20mg/kg的OMT可抑制HBV复制,并且在清除血清HBsAg和肝内HBcAg方面比恩替卡韦(ETV)更有效。此外,OMT以剂量依赖的方式促进CD4 T细胞中干扰素-(IFN-)的产生。我们的研究结果证明了OMT在增强免疫功能和控制HBV抗原方面的有益作用。这些发现表明该药物是治疗HBV感染的良好抗病毒治疗候选药物。

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