拉米夫定联合泛昔洛韦抗鸭乙型肝炎病毒的实验研究  

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

作　　者：陈压西[1] 郭树华[1] 齐珍元[1] 黄爱龙[1] 

机构地区：[1]重庆医科大学病毒性肝炎研究所,400010

出　　处：《中华肝脏病杂志》2001年第4期209-211,共3页Chinese Journal of Hepatology

基　　金：重庆市科委青年科技专家基金;重庆市教委科学技术研究项目基金

摘　　要：［目的］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（ＤＨＢ）的作用。方法采用重庆麻鸭乙型肝炎动物模型，用拉米夫定联合泛普洛韦口服治疗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。结果拉米夫定联会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ＤＨＢＶＤＮＡ含量较用药 ４周时 ＤＨＢＶ ＤＮＡ含量回升现象不明显。用药前后血清 ＤＨＢｓＡｇ的吸光度值（４９０ ｎｍ）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周后血清转氨酶检查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普洛韦连续用药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。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.

关 键 词：拉米夫定 泛昔洛韦 动物模型 乙型肝炎 药物联合治疗 抗鸭乙型肝炎病毒 DHBV 

分 类 号：R512.62[医药卫生—内科学] R978.7[医药卫生—临床医学]