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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 investigate the anti-hepatitis B virus effect of 99mTc labeled lactose polylysine lamivudine (Lac-PLL-LA). Methods The effect of Lac-PLL-LA against hepatitis B virus (HBV) was observed in vitro and in vivo respectively. ① In Vitro Level: The inhibitory rates of Lac-PLL-LA and LA against 2.2.15 cells secreting HBsAg, HBeAg and HBV DNA were compared. ② In vivo: Chronic hepatitis B virus model mice were randomly divided into four groups: normal saline control group, LA positive control group, Lac-PLL-LA50mg / kg and 100mg / kg, Administration 10d, 2 times daily before administration and after administration of 5,10 days and 3 days after withdrawal of blood, serum was isolated by dot blot hybridization and autoradiography methods to observe the mouse serum hepatitis B virus Dynamic changes of DNA (HBV-DNA). Results In vitro, the anti-HBV effect of Lac-PLL-LA serum group was better than that of LA group (HBsAg: 53.09 ± 1.09 and 40.02 ± 0.79, P <0.05; HBeAg: 54.65 ± 2.14 and 35.13 ± 0.94, P <0.01 (P <0.05); HBeAg: 55.09 ± 1.32 and 35.78 ± 0.99 (P <0.05), and the anti-HBV effect of Lac-PLL-LA serum group was better than that of LA group 0.05). Anti-HBV activity of Lac-PLL-LA at in vivo level: The OD value of serum HBV DNA of Lac-PLL-LA 50 mg / kg, 100 mg / kg at different time after administration was lower than that of model control group and LA group , And no obvious rebound phenomenon after stopping. Conclusion Lac-PLL-LA has a good effect of inhibiting HBV infection both in vitro and in vivo, and is not prone to rebound phenomenon after stopping drug treatment. It is expected to become a new anti-HBV drug.