拉米夫定联合泛昔洛韦抗鸭乙型肝炎病毒的实验研究

观察核苷酸类似物拉米夫定联合泛昔洛韦体内抗鸭乙型肝炎病毒（DHBV）的作用。方法 采用重庆麻鸭乙型肝炎动物模型，用拉米夫定联合泛昔洛韦口服治疗4周，停药观察1周，检测用药前后血清中的DHBV DNA、DHBsAg及血清转氨酶（ALT、AST）、肝组织HE染色病理。并以单用拉米夫定、泛昔洛韦、阿昔洛韦作对照。结果 拉米夫定联合泛昔洛韦用药后能使血清中DHBV DNA含量总体水平显著降低（P＜0．01），停药1周后DHBV DNA较用药4周时DHBV DNA含量回升现象不明显。用药前后清血DHBsAg的吸光度值（490nm)的变化与DNA含量改变相似；此外，肝脏病理检查及治疗4周、停药1周后血清转氨酶检测未发现联合用药对鸭肝组织有明显的毒性损害。结论 拉米夫定联合泛昔洛韦连续用药4周在鸭体内有抗鸭乙型肝炎病毒的作用，且停药后DHBV DNA无明显“反跳”，二者用药有协同作用。

Experimental study on the effect of combination therapy with lamivudine and famciclovir against duck hepatitis B virus in vivo

Objective To study the antiviral effect of combination therapy with the nucleoside analog lamivudine and famciclovir on duck hepatitis virus (DHBV) in vivo. Methods The Chongqing duck hepatitis B model was treated with lamivudine and famciclovir by intragastric administration for 4 weeks. DHBV DNA and DHBsAg in serum were observed by serum dot-blot hybridization and ELISA. ALT and AST in serum were also detected. Histological observation on the duck liver was done simultaneously. The trial was contrasted with a single acyclovir (ACV), famciclovir (FCV), or Lamivudine (3TC). Results Combination therapy with Lamivudine and famciclovir could significantly reduce the serum DHBV DNA level. After stopping the treatment for 1 week, serum DHBV DNA level did not return significantly. The change of DHBsAg was similar to DHBV DNA. The level of ALT, AST, and the features of liver histopathology in combination-treated ducks were not different from those in control ducks. Conclusions The study confirms that combination therapy is superior to single antiviral agent in vivo for ducks with chronic DHBV carrier.