乙型肝炎导向干扰素抗乙型肝炎病毒作用的体外实验研究

EXPERIMENTAL STUDIES OF THE EFFECT OF TARGETING INTERFERON WITH MONOCLONAL ANTI-HBV ANTIBODY ON HEPATITIS B VIRUS IN VITRO

为提高ＩＦＮ抗ＨＢＶ疗效，实现感染细胞水平上的抗病毒性肝炎导向治疗，我们将抗ＨＢｓＡｇ单克隆抗体（ＭｃＡｂ）的Ｆ（ａｂ＇）２片段与ＩＦＮ文联，所得交联体称为乙型肝炎导向干扰素（Ｔ－ＩＦＮ）。应用ＨＢＶＤＮＡ转染细胞系（２，２，１５细胞）作模型，对Ｔ－ＩＦＮ进行了体外抗ＨＢＶ实验：通过检测细胞上清液ＨＢｓＡｇ、ＨＢｅＡｇ和ＨＢＶＤＮＡ水平的变化，结合细胞存活率来评价其抗ＨＢＶ活性，并与游离ＩＦＮ和ＭｃＡｂ以及二者的混合法（Ｍｉｘ）进行比较。结果显示，经１２天作用，Ｔ－ＩＦＮ在细胞存活率。

lnterferon (IFN ) was a kind of generally acknowledged effective drug on anti - Hepatitis B Virus (HBV)at present, but its actual cure rate was not high,it had some adverse reactions un- dereffective dose. ln order to enhance the effect of IFN and to carry out the targeting treatment onthe infected cells , the Targeting IFN with Monoclonal Antibody Against HBV (T-IFN pared by the lnstitute of Liver Disease of PLA. Using a HBV DNA transfected cell line (2 , 2 , I5 cell line ) as the model,we examined the inhibitory effects on expression of HBsAg and HBeAg, and determined the change of HBV DNA level in supernatant fluid of cell culture, and also ob- served the cell growth and survival rate,then we evalated and compared the anti - HBV effects of T - IFN 、IFN 、Monoclonal antibody (McAb ) of anti - HBsAg and Mixture of McAb and IFN (Mix) . The results indicated that after l2 days' treatment , the anti - HBV at the concentration of 1500 - 3000IU/ml , with cell survival rate ≥ 79. 6% , the inhibitory tate of HBsAg57. 3 - 67. 7% , the inhibitory rate of HBeAg40. 1 - 51. 2%, and HBV DNA lower than 1 - 10fg,compared with HBV DNA> 1pg in the IFN McAb and Mix at the same concentration,the inhibitory rates of HB- sAg and HBeAg were lower than that of T -- IFN. lt was suggested that T-IFN might play role in several key --- links,such as viral replication and viral protein synthesis or expression. T-IFN might take advantage of interacting both receptors of IFN and HBsAg, by McAb' carried , IFN could be easier to get to the targeting cells. The results proved that targeting IFN with McAb can enhance the anti--HBV effect of IFN.