乙型肝炎表面抗原阳性转基因小鼠肝组织基因表达谱及蛋白组学的初步研究

任军1 ;赵超1 ;方彩云2 ;马张妹1 ;杨芃原2 ;闻玉梅1  

微生物与感染 ›› 2006, Vol. 1 ›› Issue (1) : 7-14.

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微生物与感染 ›› 2006, Vol. 1 ›› Issue (1) : 7-14.
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乙型肝炎表面抗原阳性转基因小鼠肝组织基因表达谱及蛋白组学的初步研究

  • 任军1;赵超1;方彩云2;马张妹1;杨芃原2;闻玉梅1 
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Transcriptomic and proteomic study of HBsAg positive transgenic mouse liver suggests that viral protein affects the hepatocellular metabolism of sugar, lipid and amino acids

  • REN Jun1;ZHAO Chao1;FANG Cai-yun2;MA Zhang-mei1;YANG Peng-yuan2;WEM Yu-mei1

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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。

Abstract

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 microarray 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.

关键词

转基因小鼠 / 基因芯片 / 蛋白组学 / 代谢

Key words

Hepatitis B virus / Transgenic mouse / DNA microarray / Proteomic / Metabolism

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任军1 ;赵超1 ;方彩云2 ;马张妹1 ;杨芃原2 ;闻玉梅1  . 乙型肝炎表面抗原阳性转基因小鼠肝组织基因表达谱及蛋白组学的初步研究

[J]. 微生物与感染. 2006, 1(1): 7-14

REN Jun1;ZHAO Chao1;FANG Cai-yun2;MA Zhang-mei1;YANG Peng-yuan2;WEM Yu-mei1

.

Transcriptomic and proteomic study of HBsAg positive transgenic mouse liver suggests that viral protein affects the hepatocellular metabolism of sugar, lipid and amino acids

[J]. Journal of Microbes and Infections. 2006, 1(1): 7-14

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