目的验证HBsAg阳性转基因小鼠肝脏中昼夜节律表达基因dbp(coding for the D site albumin promoter binding protein)转录水平的变化。方法用实时荧光定量聚合酶链式反应方法对比研究雌、雄及个体HBsAg阳性转基因小鼠及对照鼠肝脏dbp转录水平的变化。研究不同时间点HBsAg阳性转基因小鼠及对照鼠肝脏dbp转录水平的变化。结果#59及#10品系组HBsAg阳性转基因小鼠肝组织中dbp转录水平均较对照组动物上调,但个体间差别较大。初步结果显示雌性正常小鼠dbp转录水平较雄性高。而在雌性HBsAg阳性转基因小鼠中dbp上调进一步增强。与此相反,雄性转基因小鼠dbp上调则较同性对照鼠更弱。转基因小鼠dbp转录在8:00及14:00时平均水平均高于对照鼠,然而在20:00及2:00时与对照鼠相当。结论本研究首次报道HBsAg阳性转基因小鼠肝脏中dbp表达的上调,提供了乙型肝炎病毒蛋白表达与昼夜节律基因变化有所联系的证据。至于本研究在转基因鼠中的发现是否在乙型肝炎患者中存在及其意义还有待在患者中作进一步临床验证与研究。
Objective To verify alterations in the circadian gene dbp (coding for the D site albumin promoter binding protein) in liver tissues of HBsAg-positive transgenic mice. Methods Fluorescent quantitative real-time PCR was used to compare the transcriptional levels of dbp in male and female HBsAg positive transgenic mice against controls. Individual transgenic mice at different time points were used to study the regulation of dbp. Results In the liver tissues from both # 10 and # 59 lineages of HBsAg-positive transgenic mice, dbp was upregulated, compared to their control counterparts. However, there was marked individual variability. Prehminary results showed that in HBsAgnegative female mice, the transcriptional level of dbp was higher than that in male mice and this difference was even more marked in HBsAgpositive female transgenic mice. At 8:00 and at 14: 00, dbp expression was up-regulated in HBsAg-positive transgenic mice, compared to controls However, at 20:00 and 2: 00, the dbp transcriptional levels were similar between HBsAg-positive transgenic mice and controls. Conclusion This study is showing, for the first time, that dbp expression is up-regulated in HBsAg-positive transgenic mice, which provides evidence that HBV protein expression may be associated with changes in a circadian gene. Further studies are needed to confirm whether this up-regulation can also be found in htunan subjects and to clarify the implications of this observation.