一氧化氮供体药物JS-K抗乙肝病毒作用机制研究

HBV相关性疾病是当今威胁人类健康的主要疾病之一，现在的抗病毒治疗药物主要有核苷类似物及干扰素。这些药物虽有一定疗效，但也存在不良反应，而且针对核苷类似物的耐药性也逐渐增加。因此，新型抗HBV药物的研究具有更重要的意义。JS-K是一种偶氮鎓二醇盐类一氧化氮供体药物，能以谷胱甘肽-S-转移酶（GST）为靶点，与在肿瘤细胞中过表达的GST结合而释放NO，从而发挥药效作用，现多用于各种肿瘤性疾病的治疗，至今尚未见JS-K抗病毒的研究报道。本课题组在预实验中发现：在HBV能够复制并产生完整病毒颗粒的肝癌细胞株HepG2.2.15中，JS-K能抑制HBV的两个重要抗原--乙肝表面抗原(HBsAg)和e抗原(HBeAg)的表达。本研究将利用分子生物学以及细胞生物学技术，通过体内外实验研究进一步阐明JS-K抗HBV复制的效应机制及其靶标，以期为开发新的抗HBV感染治疗手段提供坚实的实验依据。

HBV-related disease is one of the major diseases threating human health. Nowadays, nucleoside analogues and interferon are the important drugs against HBV. Although,these drugs have a certain effect, there are also have some side effects, and the resistance against nucleoside analogues are increasing gradually. So, it is very important to develop new drug against HBV. JS-K, a diazeniumdiolate-based nitric oxide-releasing prodrug, designed to target overexpressed GST in tumor cells, is effective against a variety of tumor cells. It has not been reported that JS-K inhibit the replication of virus so far. We found JS-K could inhibit the secretion of HBsAg and HBeAg in HepG2.2.15 cell line, which could support persistent replication of HBV and produce intact HBV particles. This study will reveal the role and target of anti-HBV effect of JS-K in vitro and in vivo by molecular biology and cytobiology, and it could provide an alternative therapeutic approach for HBV infection.