受体导向药物L－HSA－AraAMP体外抗病毒效应的实验研究

EXPERIMENTAL STUDY ON THE ANTI-VIRAL EFFECT OF TARGETING DRUGWITH LIGAND OF H-GAL RECEPTOR IN VITRO

以乙肝病毒（ＨＢＶ）ＤＮＡ转染的细胞株２．２．１５细胞培养上清液中ＨＢｓＡｇ、ＨＢｅＡｇ滴度及细胞内ＨＢＶＤＮＡ中间体的变化作为药物评价指标，应用四甲基偶氮唑盐（ＭＴＴ）比色分析法测定细胞毒性。结果表明：乳糖化人血清白蛋白单磷酸阿糖腺苷（Ｌ－ＨＳＡ－ＡｒａＡＭＰ简称交联物）与ＡｒａＡＭＰ具有相似的抗病毒效应。二者对ＨＢｓＡｇ最高抑制率分别为５０％，６３％，对ＨＢｅＡｓ最高抑制率分别为６２．６％，６７．２％，５００μｇ／ｍｌ交联物与１００μｇ／ｍＩＡｒａＡＭＰ对ＨＢＶＤＮＡ有相似的抑制作用。交联物无明显细胞毒性（ＣＤ５０＞２０００μｇ／ｍｌ），ＡｒａＡＭＰ有明显细胞毒性（ＣＤ为６５８．５±１８０μｇ／ｍｌ），对ＨＢｅＡｇ抑制的选择指数分别为＞４．８，１．７。展示了受体导向抗病毒药物的良好前景。

This experimental study was performed on 2.2.15 cells which were HepG2 Cellstvansfec ted with HBV DNA. The efficacy of targeting drug was determined by analyzing dynamic changesin HBsAg and HBeAg in culture medium by RIA and changes in the replicative intracellular HBV DNAcontent by Southern blot. Their cytotoxicity were determined with MTT method. AraAMP was the posi-tive control drug。 No drug was the negative control group. The results showed that AraAMP demonst rated a stronger cell toxicity,its CD50 was 658.5±180(μg/ml). The values of Si of HBsAg and HBeAg were5.3 and 1. 7 respectively。 The targeting drug had indistinct cell toxicity,CD50 was higher than 2 000(μg/ml),the values of Si were>4 and>4.8. The targeting drug had significant inhibitory ratio of HBsAg andHBeAg, which was similar to that of AraAMP.Southern blot test showed that the replicative intermedi-ates RCDNA and SSDNA were inhibited by AraMAP. The targeting drug had parallel anti HBV DNAreplicative effecti veness compared with AraAMP。