| 硼替佐米对转基因小鼠原代肝细胞HBV的抑制作用 |
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| 引用本文： | 易学瑞,袁有成,陈阳述,陈文吟,陶鑫,张锋,张欣蕊,孔祥平. 硼替佐米对转基因小鼠原代肝细胞HBV的抑制作用[J]. 中国药理学通报, 2011, 27(5): 614-617. DOI: 10.3969/j.issn.1001-1978.2011.05.006 |
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| 作者姓名： | 易学瑞 袁有成 陈阳述 陈文吟 陶鑫 张锋 张欣蕊 孔祥平 |
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| 作者单位： | 1. 解放军第四五八医院全军肝病中心,广东,广州,510600
2. 解放军第四五八医院全军肝病中心,广东,广州,510600;南方医科大学,广东,广州,510515 |
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| 基金项目： | "爱滋病和病毒性肝炎等重大传染病防治"科技重大专项"十一五"课题 |
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| 摘 要： | 目的利用HBV转基因小鼠原代肝细胞评价蛋白酶体抑制剂硼替佐米的抗病毒效果。方法采用改良的两步灌流法分离HBV转基因小鼠原代肝细胞;分别采用ELISA和荧光定量PCR法检测HBsAg和HBV-DNA的水平;采用MTT法观察不同浓度的硼替佐米对HBV转基因小鼠原代肝细胞和HepG2.2.15细胞的毒性,观察其作用24 h后细胞培养上清中病毒学指标的变化。结果分离的原代肝细胞纯化后活细胞占0.90,HBsAg和HBV-DNA在5 d内均能稳定表达。药物作用24 h后,MTT结果显示260μmol·L-1及以下浓度的硼替佐米对原代肝细胞无明显毒性,但对HepG2.2.15细胞显示较强的细胞毒性,其最大无毒浓度为12.5 nmol·L-1。药物在0.026μmol·L-1～26μmol·L-1的浓度范围内对转基因小鼠原代肝细胞HBsAg和HBV-DNA有明显抑制作用。结论硼替佐米在体外对HBV有抑制作用;HBV转基因小鼠原代肝细胞可用于抗肿瘤药物的抗HBV活性研究。
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| 关 键 词： | 硼替佐米 蛋白酶体抑制剂 HBV转基因小鼠 原代肝细胞 乙型肝炎病毒 乙肝表面抗原 HBV-DNA |
Bortezomib inhibits hepatitis B virus replication on primary hepatocytes of HBV transgenic mice |
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| YI Xue-rui,YUAN You-cheng,CHEN Yang-shu,CHEN Wen-yin,TAO Xin,ZHANG Feng,ZHANG Xin-rui,KONG Xiang-ping. Bortezomib inhibits hepatitis B virus replication on primary hepatocytes of HBV transgenic mice[J]. Chinese Pharmacological Bulletin, 2011, 27(5): 614-617. DOI: 10.3969/j.issn.1001-1978.2011.05.006 |
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| Authors: | YI Xue-rui YUAN You-cheng CHEN Yang-shu CHEN Wen-yin TAO Xin ZHANG Feng ZHANG Xin-rui KONG Xiang-ping |
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| Affiliation: | YI Xue-rui1,YUAN You-cheng1,CHEN Yang-shu1,CHEN Wen-yin1,TAO Xin1,2,ZHANG Feng1,ZHANG Xin-rui1,KONG Xiang-ping1(1.the Liver Center of PLA,N0.458 Hospital of PLA,Guangzhou 510600,China,2.Southern Medical University,Guangzhou 510515,China) |
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| Abstract: | Aim To evaluate the anti-HBV effect of proteasome inhibitor-bortezomib with primary hepatocytes isolated from HBV transgenic mice(HBV-Tg mice).Methods The primary hepatocytes was separated from HBV-Tg mice with the modified two-steps method;HBsAg and HBV-DNA in the supernatant of the cell culture were examined with ELISA and real-time PCR to observe the function of HBV replication and expression in primary hepatocytes of HBV-Tg mice.The cytotoxicities of bortezomib on the primary hepatocytes and HepG2.2.15 ... |
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| Keywords: | HBV-DNA |
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