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苯丙氨酸二肽类化合物073对鸭乙型肝炎病毒DNA的抑制作用
引用本文:徐颖,黄正明,徐必学,邱净英,梁光义.苯丙氨酸二肽类化合物073对鸭乙型肝炎病毒DNA的抑制作用[J].中国新药与临床杂志,2010(3).
作者姓名:徐颖  黄正明  徐必学  邱净英  梁光义
作者单位:中国人民解放军302医院药学部药理研究室;贵州省-中国科学院天然产物化学重点实验室;
基金项目:国家科技部“国际合作”新药基金项目(2008DFB30110); 国家自然科学基金项目(30760292); 贵州省中药现代化项目(黔科合农字[2006]5001号); 973计划前期研究专项资助(2007CB516800)
摘    要:目的观察苯丙氨酸二肽类化合物073对雏鸭乙型肝炎病毒DHBV-DNA的抑制效果。方法90只感染DHBV的北京雏鸭,随机分为5组:对照组,苯丙氨酸二肽类化合物073低、中、高剂量组(0.025g·kg-1、0.05g·kg-1和0.1g·kg-1)和拉米夫定组(0.05g·kg-1)。于给药前、给药d7、d14及停药后d3,各组雏鸭腿静脉取血,分离血清,样品点膜,标记DHBV-DNA探针,血清斑点杂交,放射自显影膜片斑点检测。以杂交斑点吸光度值进行自身和组间比较,并作鸭肝组织病理检查评价。结果苯丙氨酸二肽类化合物073低、中、高剂量组能明显降低鸭血清DHBV-DNA水平,给药d7、d14及停药后d3的抑制率与对照组比较,均有非常显著差异(P<0.01)。肝组织病理检查发现对照组鸭肝细胞的变性坏死较重,而苯丙氨酸二肽类化合物073中、高剂量组则较轻。结论苯丙氨酸二肽类化合物073对DHBV-DNA有明显的抑制作用,而且有保护肝细胞的作用。

关 键 词:苯丙氨酸  肝炎病毒  乙型    模型  动物  苯丙氨酸二肽类化合物073

Effect of phenylalanine dipeptide compounds 073 on duck hepatitis B virus
XU Ying,HUANG Zheng-ming,XU Bi-xue,QIU Jing-ying,LIANG Guang-yi.Effect of phenylalanine dipeptide compounds 073 on duck hepatitis B virus[J].Chinese Journal of New Drugs and Clinical Remedies,2010(3).
Authors:XU Ying  HUANG Zheng-ming  XU Bi-xue  QIU Jing-ying  LIANG Guang-yi
Institution:XU Ying1,HUANG Zheng-ming1,XU Bi-xue2,QIU Jing-ying2,LIANG Guang-yi2 (1. Department of Pharmacology of Pharmacy,302 Hospital of PLA,BEIJING 100039,China,2. The Key Laboratory of Chemistry for Natural Products,Guizhou Province , Chinese Academy of Sciences,Guiyang GUIZHOU 550002,China)
Abstract:AIM To observe the inhibitive effect of phenylalanine dipeptide compounds 073 (PDC073) on nestling duck hepatitis B virus (DHBV) model. METHODS Ninety infected nestling ducks with positive serum DHBV created as models were randomly divided into saline control group, PDC073 (0.025 g·kg-1, 0.05 g. kg-1, 0.1 g·kg-1) groups, and positive drug lamivudine control (0.05 g·kg-1) groups, as well as the normal group. Drugs were given orally. The blood samples were taken from leg vein and separated the serum for labels before the treatment, d 7, d 14 after treatment, and d 3 after treatment. The presence of DHBV-DNA inserum was detected by dot blot hybridization. Probe was labeled with 32 P. Liver biopsy was also performed before and after the treatment for demonstrating the histopathological changes. RESULTS The low, middle and high dosage groups of PDC073 showed decrease levels of the infected ducks serum DHBV-DNA comparing with those of the control group, revealing significant difference (P < 0.01) . The histopathological damage of liver tissues showed that the inflammation in the middle and high dosage groups of PDC073 was apparently lesser than that of the control group. CONCLUSION The PDC073 provides obviously inhibitive effect on DHBV-DNA and protection for liver in vivo.
Keywords:phenylalanine  hepatitis B virus  duck  models  animal  phenylalanine dipeptide compounds 073  
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