复方药物ZL-1在鸭乙型肝炎病毒实验感染模型中抗病毒作用的研究

Anti-viral study of a Chinese herbal medicine ZL-1 in experimentally DHBV infected animal model

目的 研究中药复方ZL 1在鸭乙型肝炎病毒 (DHBV)持续性感染模型中抗嗜肝DNA病毒的作用。方法应用中药复方ZL 1治疗实验感染鸭 ,口服给药 ,剂量 5 0 0mg·kg-1·d-1,分 2次服用 ,连续 4周。采用斑点分子杂交和Southern印迹杂交检测治疗后感染鸭血清和肝脏中病毒的动态变化。同时以拉米夫定及安慰剂作为对照组。结果 复方药物ZL 1治疗后血清中DHBVDNA均数从 3 .6× 10 10 拷贝 /ml下降至 0 .9× 10 10 拷贝 /ml(P <0 .0 1) ,抑制病毒率为 75 % ,但尚不能清除病毒血症 ,肝组织中总DHBVDNA和DHBV超螺旋型DNA量无明显减少 ,停药观察 2周 ,病毒复制反弹不明显。拉米夫定治疗后可显著降低病毒血症 (P <0 .0 1) ,抑制病毒率达 99% ,同时肝组织中总DHBVDNA和DHBV超螺旋型DNA量减少 ,但停药观察 2周 ,病毒复制反弹明显。安慰剂组 (口服生理盐水 )治疗前后病毒水平的差异无显著性 (P >0 .0 5 )。结论 复方药物ZL 1治疗4周可使感染鸭病毒血症降低 ,但不能清除病毒血症 。

Objective To study the anti-hepadna virus effect of a Chinese herbal medicine ZL-1 in DHBV infected animal model. Methods The DHBV infected ducks were treated with ZL-1 orally at a dosage of 500 mg·kg -1·d -1, twice a day for 4 weeks. DHBV DNA in serum and liver of DHBV infected ducks were detected by using dot blot and Southern blot hybridization. Results In ZL-1 treated ducks, the serum DHBV DNA declined from 3.6×10 10 copy/ml to 0.9×10 10 copy/ml (P<0.01), and the inhibition rate of DHBV reached 75%, but the total viral DNA and cccDNA in the liver were not affected significantly. After cessation of the treatment for two weeks, no rebound of DHBV DNA in serum was observed. In Lamivudine (25mg/kg, once a day) treated ducks, DHBV DNA in serum declined sharply (P<0.01) and in 4/6 ducks appeared below the detectable level; and the inhibition rate of DHBV reached 99%. The total DHBV DNA and cccDNA in the liver was also decreased. However, after that the DHBV DNA viral load was resurged significantly. In the saline treated DHBV infected ducks, no changes of DHBV DNA in serum and liver were obsvered (P>0.05). In noninfected ducks, no viremia was detected. Conclusion ZL-1 can decrease serum DHBV DNA level, but can not clear the viremia and the replication of DHBV in the liver.