拉米夫定与单磷酸阿糖腺苷联合应用抗-HBV的体外实验研究

目的　体外观察拉米夫定 (3TC)与单磷酸阿糖腺苷 (Ara AMP)联合应用的抗 HBV作用。方法　以 2 2 15细胞为靶细胞 ,实验共进行 8d。采用放射免疫法及斑点杂交测定单用 3TC、Ara AMP及联合应用后对培养上清液HBsAg、HBeAg及细胞内HBVDNA的抑制作用。结果　Ara AMP浓度为40 0 0 μg ml时 ,对HBsAg、HBeAg的抑制作用分别为 45 48%和 41 46 %。 3TC在所取浓度范围内虽然对HBsAg和HBeAg也有一定的抑制作用 ,但抑制作用较弱。Ara AMP 5 0 0 μg ml与 3TC 1 2 5和 5 0 0μg ml联合应用 ,对HBsAg的抑制率分别可达 19 92 %和 17 32 %。其HBsAg含量与单用相同浓度的3TC相比 ,差异有显著意义 (P <0 0 5 ) ,但与单用相同浓度的Ara AMP相比 ,差异无显著意义 (P <0 0 5 )。联合用药对HBeAg无明显抑制作用。 3TC 5 0 0 μg ml与Ara AMP 12 5和 5 0 0 μg ml联合应用 ,对HBVDNA抑制率可达 45 90 %和 5 0 36 %。HBVDNA含量与阴性对照组及单用相同浓度的 3TC、Ara AMP组相比 ,差异有显著意义 (P <0 0 5 )。结论　 3TC与Ara AMP联合应用对HBVDNA的抑制作用明显增强

In vitro evaluation on the effects of combined lamivudine(3TC) and Ara-AMP against hepatitis B virus

BACKGROUND: To evaluate the inhibitive effect of combination of 3TC with Ara-AMP against HBV in vitro. METHODS: Used 2.2.15 cell as target cell. With radioimmunological technique and blot slot, the inhibitive effect of 3TC, Ara-AMP and the combination of both against the HBsAg, HBeAg and intracellular HBV DNA were investigated. RESULTS: The inhibitive ratio of Ara-AMP against HBsAg, HBeAg was 45.48% and 41.46% respectively when its concentration was 400.0 microgram/ml. Although 3TC also has inhibitive effect in its experimental concentration, its effect is weaker. When Ara-AMP 50.0 microgram/ml was combined with 3TC 1.25 and 5.00 microgram/ml respectively, the inhibitive ratio against HBsAg were 19.92% and 17.32% respectively. Compared with using same concentration 3TC alone, the difference of results was significant (P<0.05). But when compared with using the same concentration Ara-AMP alone, the difference of results had no statistical significance (P <0.05). Remarkable inhibitive effects of combination of 3TC with Ara-AMP against HBeAg were n ot found. When 3TC 5.00 microgram/ml was combined with Ara-AMP 12.5 and 50.0 microgram/ml respectively, the inhibitive ratio against HBV DNA was 45.90% and 50.36% respectively. Comparing the content of HBV DNA in these groups with that of control group and the groups using the same concentration 3TC and Ara-AMP alone, the differences were significant (P <0.05). CONCLUSIONS: Combination of 3TC with Ara-AMP could enhance the inhibitive effects against HBV DNA.