重组人干扰素α-2b对丙型肝炎患者血清铁调素的影响及其机制

摘要/Abstract

摘要： 目的探讨重组人干扰素α-2b(IFNα-2b)对丙型肝炎患者血清铁调素(Hepcidin)的影响及其机制。方法选择2020年1月至2023年1月丙型肝炎患者35例,按近3个月是否接受IFNα-2b治疗分为治疗组(n=20)和未治疗组(n=15),检测2组血清Hepcidin水平。另用0、50、100、200、400 μL五种不同剂量的IFNα-2b处理HepG2细胞24 h。分别检测血清Hepcidin、信号转导与转录激活子 3(STAT3)及磷酸化 STAT3(pSTAT3)的mRNA表达量。结果治疗组血清Hepcidin为(94.91 ± 16.28)ng/mL,明显低于未治疗组的(107.99±17.06)ng/mL,差异有统计学意义(t=4.396,P<0.05)。IFNα-2b剂量为0、50、100、200、400 μL时,HepG2细胞的Hepcidin mRNA表达分别为1.00±0.23、0.67±0.12、0.28±0.04、0.25±0.03、0.17±0.02,呈递减趋势,各组Hepcidin mRNA表达差异均有统计学意义(P<0.05)。组间两两比较,400 μL低于0、50、100、200 μL;100、200 μL低于0、50 μL;50 μL低于0 μL,差异均有统计学意义(P<0.05)。0、50、100、200、400 μL HepG2细胞的STAT3 mRNA表达水平分别为0.72±0.11、0.74±0.12、0.68±0.09、0.66±0.06、0.66±0.08,差异均无统计学意义(P>0.05)。50、100、200、400 μL剂量的IFNα-2b的PSTAT3蛋白水平分别为0.76±0.14、0.65±0.06、0.57±0.07、0.54±0.05均低于0 μL的(0.85±0.16),差异有统计学意义(P<0.05),50、100、200、400 μL剂量的IFNα-2b的PSTAT3蛋白水平比较差异均无统计学意义(P>0.05)。结论丙型肝炎患者IFNα-2b治疗后血清Hepcidin水平会下调,且下调幅度与剂量有关,其机制可能与STAT3通路磷酸活化受阻有关。

关键词: 重组人干扰素α-2b, 丙型肝炎, 铁调素, 机制

Abstract: Objective To investigate the impact of recombinant human interferon-α2b(rhIFN-α2b) on serum hepcidin levels in hepatitis C patients, and to preliminarily explore its imderlying mechanism. Methods A total of 35 hepatitis C patients from January 2020 to January 2023 were selected and divided into a treatment group (n=20) and an untreated group (n=15) based on whether they received rhIFN-α2b treatment in the last 3 months. Serum hepcidin levels were measured in both groups. Additionally, serum hepcidin, signal transducer and activator of transcription 3 (STAT3), and its phosphorylation(pSTAT3) were measured in hepatogenic HepG2 cells treated with 0, 50,100, 200, and 400ul of rhIFN-α2b for 24 hours. Changes in mRNA expression of STAT3 and correlation analyses were performed. Results Serum hepcidin levels in the treated group was significantly lower (94.91 ± 16.28) ng/mL compared to the untreated group (107.99±17.06) ng/mL, with the difference being statistically significant (t=4.396, P<0.05). HepG2 cells treated with rhIFN-α2b at doses of 0 μL (control group), 50 μL (group 1), 100 μL (group 2), 200 μL (group 3), and 400 μL (group 4) exhibited a dose-dependent decrease in hepcidin. mRNA expression: (1.00±0.23), (0.67±0.12), (0.28±0.04), (0.25±0.03), and (0.17±0.02), respectively. The differences in hepcidin mRNA expression among all groups were statistically significant (P<0.05). Pair comparisons showed that group 4 (400 μL) had significantly lower hepcidin mRNA levels than the control group, group 1, group 2 and group 3. Groups 2 and 3 also had significantly lower levels compared to the control group and group 1. Group 1had significantly lower levels than the control group (P<0.05). STAT3 mRNA expression levels in HepG2 cells for the control group, group 1, group 2, group 3, and group 4 were (0.72±0.11), (0.74±0.12), (0.68±0.09), (0.66±0.06), and (0.66±0.08), respectively, with no statistical differences(P>0.05). The pSTAT3 protein levels for rhIFN-α2b at doses of 50 μL, 100 μL, 200 μL , and 400 μL were (0.76±0.14), (0.65±0.06), (0.57±0.07), and (0.54±0.05), respectively, all lower than the control group. However, there were no significant differences in pSTAT3 protein levels among the treated groups (P>0.05). Conclusion After rhIFN-α2b treatment, the serum hepcidin levels in hepatitis C patients are down-regulated in a dose-dependent manner. This down-regulation may be associated with the inhibition of phosphorylation activation in the STAT3 pathway.

Key words: Recombinant human interferon -α2b, Hepatitis C, Hepcidin, Mechanism

王雪梅, 宫富琪, 郑金娜, 于燕民, 徐菁, 杨永生. 重组人干扰素α-2b对丙型肝炎患者血清铁调素的影响及其机制[J]. 肝脏, 2024, 29(7): 840-843.

WANG Xue-mei, GONG Fu-qi, ZHENG Jin-na, YU Yan-min, XU Jing, YANG Yong-sheng. Impact of recombinant human interferon- α2b on serum hepcidin levels in hepatitis C patients: underlying mechanism[J]. Chinese Hepatolgy, 2024, 29(7): 840-843.

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