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乳糖化多聚赖氨酸拉米呋啶的抗HBV作用研究

A Study on Anti-HBV Effect of Lactose Poly-L-Lysine Lamivudine
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摘要 目的探讨核素99mTc标记的乳糖化多聚赖氨酸拉米呋啶(简称Lac-PLL-LA)的抗乙型肝炎病毒作用。方法分别通过体外和体内水平观察Lac-PLL-LA的抗乙肝病毒作用。①体外水平:比较观察Lac-PLL-LA和LA对2.2.15细胞分泌的HBsAg、HBeAg及HBV DNA的抑制率。②体内水平:将成功建立的慢性乙型肝炎病毒模型小鼠随机分为四组,分别为生理盐水对照组、LA阳性对照组、Lac-PLL-LA50mg/kg和100mg/kg,各组均连续给药10d,每日2次,于给药前和给药后第5、10天以及停药后第3天采血,分离血清,采用斑点杂交方法及放射自显影方法,观察小鼠血清乙肝病毒DNA(HBV-DNA)的动态变化。结果体外水平:作用5d时,Lac-PLL-LA血清组抗HBV作用优于LA组(HBsAg:53.09±1.09和40.02±0.79,P<0.05;HBeAg:54.65±2.14和35.13±0.94,P<0.01);药物作用10d时,含Lac-PLL-LA血清组抗HBV作用均优于LA组(HBsAg:54.97±2.01和58.17±1.28,P<0.05;HBeAg:55.09±1.32和35.78±0.99,P<0.05)。体内水平上Lac-PLL-LA的抗乙肝病毒作用:Lac-PLL-LA 50 mg/kg、100mg/kg在给药后不同时间小鼠血清HBV DNA的OD值均低于模型对照组和LA组,且在停药后未见明显反跳现象。结论Lac-PLL-LA在体内、外均有良好的抑制HBV感染作用,且停药后不易出现反跳现象,有望成为一种新的抗-HBV作用的药物。 Objective To explore effects of Lactose poly-L-lysine Lamivudine (Lac-PLL-LA) on hepatitis B virus (HBV). Methods Anti-HBV effects of Lamivudine and Lac-PLL-LA were detected by in vitro and in vivo assay. The inhibition effect of Lac-PLL-LA and LA secretion of HbsAg and HBeAg and level of HBV DNA in 2.2.15 cells were compared. A rat model of chronic HBV was established successfully. SD model rats were randomly divided into four groups(model group, LA positive control group, Lac-PLL-LA 50 mg/kg group and Lac-PLL-LA 100 mg/kg group). All the four groups were treated for 10 days, twice a day. After oral treated for 5 days, 10 days and stop treatment, dynamic alteration of serum hepatitis virus B DNA level were detected by dot blot hybridization. Results The in vitro Anti-HBV effect of Lactose poly-L-lysine Lamivudine (HBsAg: 53.09±1.09 vs 40.02±0.79, P〈 0.05) was significant higher than that of Lamivudine (HBeAg: 54.65±2.14 vs 35.13±0.94,P〈 0.01 ) after treatment for 5 days and also after 10 days (HBsAg: 54.97±2.01 vs 58.17±1.28, P〈0.05) (HBeAg: 54.97±2.01 vs 58.17±1.28, P〈 0.05). The serum HBV DNA level of Lac-PLL-LA group was significantly lower than those of LA and saline control group, and there was no significant rebound phenomena after stop treatment. Conclusion The above results suggested Lac-PLL-LA could effectively inhibit the antigen expression and DNA replication of HBV. Lac-PLL-LA may be a potential new anti HBV drug in future.
出处 《热带医学杂志》 CAS 2008年第7期649-651,共3页 Journal of Tropical Medicine
基金 山东省教育厅资助项目(No.J05L16)
关键词 拉米呋啶 乙型肝炎病毒 Lactose poly-L-lysine Lamivudine HBV
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