摘要
目的利用与乙型肝炎病毒(ItBV)携带者相类似的#59系HBV转基因小鼠动物模型研究乙型肝炎表面抗原(HBsAg)蛋白对肝组织生理、代谢状态的影响,以了解HBsAg持续表达对肝细胞影响的机制。方法用Affmertix基因芯片观察转基因小鼠肝组织基因表达谱的改变。用蛋白组学方法鉴定部分代谢相关酶类在转基因小鼠肝组织内的丰度改变。结果基因芯片实验显示43个基因在转基因小鼠肝组织内显著(≥2倍)上调表达,104个基因显著下调表达。蛋白组学实验检出18个代谢相关酶在转基因小鼠肝组织内丰度高于对照鼠1．5倍以上,9个代谢相关酶低于对照鼠1．5倍以上。结论HBV蛋白的存在对宿主肝组织代谢状态产生显著影响。推测其表现为胆固醇合成增强、胆汁酸合成减弱。糖异生作用增强、糖酵解减弱。氨基酸分解代谢增强、尿素合成减弱。
Objective Utilize the transgenic mouse lineage # 59 which mimics human HBsAg positive carriers, to investigate mechanisms of cellular response involved in HBsAg persistence. Methods Affymertix DNA micmarray was used to observe the differential gene expression of the transgenic mouse liver compared to the sibling controls which were HBsAg negative. Proteomic experiments were conducted to identify the alterations of enzymes involved in metabolism in e transgenic mouse liver. Results Microarray showed that 43 genes were significantly （≥ 2 folds）UP regulated and 104 genes were significantly down regulated in the transgenic mouse liver. Eighteen enzymes associated with metabolisms were identified by proteomic studies with increased levels （ ≥ 1.5 folds） and 9 enzymes with decreased levels in the transgenic mouse liver. Conclusion The persistence of HBsAg markedly affected host liver cell metabolism. Specifically, cholesterol biosynthesis was increased while bile acid synthesis was diminished. While glycolysis activity was reduced, the gluconeogenesis activity was increased. Amino acid catabolism was increased and urea synthesis was decreased. The potential biological impact of these metabolic alterations in HBV persistent infection was discussed.
出处
《微生物与感染》
2006年第1期7-14,44,共9页
Journal of Microbes and Infections
基金
上海市科学技术委员会科研计划项目(05JC14008)
