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益肝清毒颗粒联合阿德福韦酯抑制鸭乙肝病毒反弹

Study on the therapeutic effects of an extract of herb medicines, YiGanQingDuKeLi, in combination with adefovir dipivoxil on the rebound of duck hepatitis B virus multiplication

摘要目的:研究益肝清毒颗粒联合阿德福韦酯( ADV)对ADV停药后鸭乙肝病毒( DHBV)感染模型体内乙肝病毒反弹的抑制作用。方法用鸭乙肝病毒阳性血清感染雏鸭7d后,实时荧光定量PCR筛选出DHBV阳性鸭,并随机分成5组,分别设为模型对照组、ADV组、中药替换组、联合给药高剂量组以及联合给药低剂量组。 ADV组持续给予ADV(0.25 mg/ml)21 d,然后停药继续饲养14 d;中药替换组持续给予ADV(0.25 mg/ml)21 d后换用益肝清毒颗粒(1.2 g/ml)再持续给药14 d;联合给药高剂量组同时给予益肝清毒颗粒(1.2 g/ml)和ADV(0.25 mg/ml)21 d后再单独使用益肝清毒颗粒(1.2 g/ml)持续治疗14 d;联合给药低剂量组同时给予益肝清毒颗粒(0.6 g/ml)和ADV (0.125 mg/ml)持续治疗21 d后单独使用益肝清毒颗粒(0.6 g/ml)持续治疗14 d。各组分别于给药后0 d、7 d、14 d、21 d及停用ADV后7 d、14 d,自腿静脉取血,检测血清中DHBV-DNA滴度以及谷丙转氨酶( ALT)和谷草转氨酶( AST)含量。结果停用ADV前,中药替换组、联合给药高剂量组和联合给药低剂量组与模型组比较,血清中DHBV-DNA、ALT和AST均显著降低(P<0.01或P<0.05),而且联合给药高剂量组较ADV组血清中DHBV-DNA含量更低。 ADV停药后, ADV组血清中DHBV-DNA、ALT和AST均出现严重反弹。与ADV组比较,中药替换组和联合给药高剂量组仍能维持在较低水平(P<0.01或P<0.05),而联合给药低剂量组虽然DHBV-DNA和ALT出现一定反弹,但仍处于较低水平(P<0.01或P<0.05)。结论益肝清毒颗粒联合ADV能有效抑制体内乙肝病毒,同时能显著抑制ADV停药后病毒的反弹。

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abstractsAbstract] Objective To investigate the in vivo therapeutic effects of an extract of herb medi-cines, YiGanQingDuKeLi, in combination with adefovir dipivoxil (ADV) on the rebound of duck hepatitis B virus ( DHBV) multiplication after withdrawal of ADV treatment.Methods Peking ducks were infected with DHBV positive serum samples for 7 days and then screened by SYBR Green real-time PCR.The ducks positive for DHBV were randomly divided into five groups including the model control group, the ADV treat-ment group, the herb treatment group, the high-dose combination therapy group and the low-dose combina-tion therapy group.The ducks in the ADV treatment and the herb treatment groups were respectively treated with distilled water and YiGanQingDuKeLi (1.2 g/ml) for 14 days after the treatment of ADV (0.25 mg/ml) for 21 days.The ducks in the high-dose group were treated with YiGanQingDuKeLi (1.2 g/ml) for 14 days after the combined treatment with high-dose YiGanQingDuKeLi (1.2 g/ml) and ADV (0.25 mg/ml) for 21 days.The ducks in the low-dose group were treated with YiGanQingDuKeLi (0.6 g/ml) for 14 days after the combined treatment with YiGanQingDuKeLi (0.6 g/ml) and ADV (0.125 mg/ml) for 21 days.Blood samples were collected from each duck via leg vein after 0, 7, 14 and 21 days of drug adminis-tration and after 7 and 14 days of drug withdrawal.The levels of DHBV-DNA, alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) in blood serum samples were detected.Results Compared with the model group, the levels of DHBV-DNA, ALT and AST in ducks from the herb treatment group and combined treatment groups were decreased before the discontinuation of ADV treatment ( P<0.05 or P<0.01).Moreover, the titers of DHBV-DNA in ducks treated with high doses of drugs were much lower than those from ADV treatment group.The levels of DHBV-DNA, ALT and AST in ducks treated with herb medi-cine and high doses of drugs remained at relatively low levels after the cessation of ADV treatment, but re-bounded significantly in ducks with ADV treatment.The levels of DHBV-DNA and ALT rebounded slightly in ducks treated with low doses of drugs as compared with those of ADV treatment group ( P<0.01 or P<0.05).Conclusion The treatment of YiGanQingDuKeLi in combination with ADV could inhibit not only the in vivo replication of DHBV, but also the rebound of DHBV multiplication after ADV withdrawal.

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作者 潘昕 [1] 时宇静 [2] 张庆华 [3] 肖汉卿 [3] 孟凤仙 [4] 图娅 [4] 费宇彤 [4] 崔晓兰 [5] 学术成果认领
栏目名称 基础免疫学
DOI 10.3760/cma.j.issn.0254-5101.2015.02.005
发布时间 2015-04-23
基金项目
国家科技部重大新药创制
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