Hou Shu-Wen, Wang Zhao-Fei, Guan Shi-He, Yang Kai, Wang Qin, Chen Li-Wen, Zhang Hao, Wang Xiu, Duan Yuan-Li, Pan Zheng-Lan
Clin Lab. 2019 Apr 1;65(4). doi: 10.7754/Clin.Lab.2018.180914.
It is unclear whether hepatitis B virus (HBV) itself causes iron metabolism disorder in patients with chronic hepatitis B (CHB). In this study, we investigated the effect of HBV on iron metabolism at the clinical and cellular levels to determine the pathogenesis of CHB.
We enrolled 41 CHB patients and 20 healthy controls (HCs) in a retrospective study. Parameters of iron status included serum iron (SI), ferritin (SF), transferrin (TRF), soluble transferrin receptor (sTfR), transferrin saturation (TS), total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), and hepcidin. Liver function indicators included serum alanine transaminase (ALT) and albumin. Furthermore, we investigated the correlations between iron markers and liver function indicators. Finally, the alterations in SF, TRF, transferrin receptor (TfR), and hepcidin expression were detected by RT-PCR, western blot, and cell immunofluorescence after HepG2 cells and Huh7 cells were transfected with the pSM2-HBV plasmid. We also measured these alterations between HepG2 cells and HepG2.215 cells. The significance of differences was analyzed by SPSS version 17.0.
Compared with healthy controls, the CHB patients were more likely to have lower levels of serum hepcidin, TRF, sTfR, TIBC, and UIBC and higher levels of SI, SF, and TS (p < 0.05, all). In CHB patients, the levels of SI and SF correlated positively with ALT concentrations, and the serum hepcidin concentrations correlated positively with albumin concentrations (p < 0.05, all). The expression levels of ferritin, transferrin, and hepcidin mRNA and protein were significantly higher in HepG2.215 cells than in HepG2 cells, while expression levels of TfR were lower. The alterations in these iron markers in HepG2 and Huh7 cells that were transfected with pSM2-HBV plasmid were consistent with those in HepG2.215 cells.
Serum iron markers tended to be abnormal in CHB patients. In hepatocytes, HBV promoted the expression of ferritin, transferrin, and hepcidin, while it inhibited the expression of TfR.
目前尚不清楚乙型肝炎病毒（HBV）本身是否会导致慢性乙型肝炎（CHB）患者出现铁代谢紊乱。在本研究中，我们在临床和细胞水平上研究了HBV对铁代谢的影响，以确定CHB的发病机制。
我们纳入了41例CHB患者和20例健康对照（HCs）进行一项回顾性研究。铁状态参数包括血清铁（SI）、铁蛋白（SF）、转铁蛋白（TRF）、可溶性转铁蛋白受体（sTfR）、转铁蛋白饱和度（TS）、总铁结合力（TIBC）、不饱和铁结合力（UIBC）和铁调素。肝功能指标包括血清丙氨酸转氨酶（ALT）和白蛋白。此外，我们研究了铁标志物与肝功能指标之间的相关性。最后，在将pSM2-HBV质粒转染到HepG2细胞和Huh7细胞后，通过逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法和细胞免疫荧光检测SF、TRF、转铁蛋白受体（TfR）和铁调素表达的变化。我们还测量了HepG2细胞和HepG2.215细胞之间的这些变化。采用SPSS 17.0版分析差异的显著性。
与健康对照相比，CHB患者血清铁调素、TRF、sTfR、TIBC和UIBC水平较低，而SI、SF和TS水平较高（均p<0.05）。在CHB患者中，SI和SF水平与ALT浓度呈正相关，血清铁调素浓度与白蛋白浓度呈正相关（均p<0.05）。HepG2.215细胞中铁蛋白、转铁蛋白和铁调素mRNA及蛋白的表达水平显著高于HepG2细胞，而TfR的表达水平较低。用pSM2-HBV质粒转染的HepG2和Huh7细胞中这些铁标志物的变化与HepG2.215细胞中的变化一致。
CHB患者血清铁标志物往往异常。在肝细胞中，HBV促进铁蛋白、转铁蛋白和铁调素的表达，而抑制TfR的表达。
