上海交通大学学报（医学版）

›› 2013, Vol. 33 ›› Issue (1): 56-.doi: 10.3969/j.issn.1674-8115.2013.01.011

• 论著（临床研究） • 上一篇    下一篇

骨髓增生异常综合征患者骨髓铁调素水平的研究

顾树程1, 宋晓丽2, 赵佑山1, 郭 娟1, 赵俊功2, 常春康1, 李 晓1   

  1. 上海交通大学附属第六人民医院 1.血液科, 2.放射科, 上海 200233
  • 出版日期:2013-01-28 发布日期:2013-02-06
  • 通讯作者: 常春康, 电子信箱: changchunkang7010@yahoo.cn。
  • 作者简介:顾树程（1987—）, 男, 硕士生；电子信箱: gscshxh@163.com。

Study of hepcidin level in bone marrow in patients with myelodysplastic syndromes

GU Shu-cheng1, SONG Xiao-li2, ZHAO You-shan1, GUO Juan1, ZHAO Jun-gong2, CHANG Chun-kang1, LI Xiao1   

  1. 1.Department of Hematology, 2.Department of Radiology, the Sixth People´s Hospital, Shanghai Jiaotong University, Shanghai 200233, China
  • Online:2013-01-28 Published:2013-02-06

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摘要：

目的 研究铁调素及其相关因素对骨髓增生异常综合征（MDS）患者铁过载水平的评估价值。方法 选取64例MDS患者，采用ELISA法对患者的外周血和骨髓铁调素水平进行测定；Real-Time PCR法测定骨髓生长分化因子15（GDF15）和扭转原肠胚形成同系物1（TWSG1）mRNA的表达；流式细胞仪对T淋巴细胞亚型（CD4+、CD19+）和极化进行测定；采用磁共振成像T2*（MRI T2*）技术对心脏和肝脏铁沉积程度进行测定；结合患者的血清铁蛋白（SF）、C反应蛋白（CRP）和促红细胞生成素（EPO）资料，对数据进行分析。结果 64例MDS患者外周血与骨髓的铁调素表达水平无明显差异（P=0.134）。根据WHO 2008分型分组，难治性贫血伴环形铁粒幼细胞增多（RARS）亚型的骨髓铁调素表达水平最低[（105.40±5.13）ng/mL]，难治性贫血伴原始细胞增多（RAEB）亚型的骨髓铁调素表达水平最高[（335.71±25.16）ng/mL]，各组间比较差异有统计学意义（P=0.041）。根据IPSS积分和WPSS积分分组，低危组和高危组骨髓铁调素表达水平比较差异均有统计学意义（P<0.05和P<0.01）；但与WPSS低危组相比，WPSS高危组的SF和GDF15 mRNA均明显高表达（P<0.05），而IPSS低危组与高危组比较差异无统计学意义（P>0.05）。根据T淋巴细胞亚型和极化分组，CD4+高表达组骨髓铁调素水平较正常组高（P<0.05）；CD19+高表达和正常组间骨髓铁调素水平比较无统计学意义（P=0.206）；Th1/Th2>70.6组骨髓铁调素水平高于Th1/Th2≤70.6组（P<0.001）。将铁调素与SF、心脏T2*值、肝脏铁浓度（LIC）（由肝脏T2*值换算得到）做逐步回归分析，仅有LIC水平与铁调素存在相关性（r=0.582，P<0.001）。结论 炎症对于调节铁调素表达至关重要，T淋巴细胞的活化及极化趋势可能在其中起到部分作用。MRI T2*对于评估MDS患者铁过载水平的效能优于SF。

关键词: 铁调素, 炎症, 磁共振成像T2*

Abstract:

Objective To determine the role of hepcidin and related factors in evaluation of iron overload in patients with myelodysplastic syndromes (MDS). Methods Sixty-four patients with MDS were enrolled. The hepcidin levels in peripheral blood and bone marrow were measured by ELISA, the expression of growth differentiation factor 15 (GDF15) and twisted gastrulation 1 (TWSG1) mRNA was detected by Real-Time PCR, T lymphocyte subtypes (CD4+ and CD19+ lymphocytes) and T lymphocyte polarization were determined by flow cytometry, the deposition of iron in heart and liver was examined through magnetic resonance imaging T2* (MRI T2*), and serum ferritin (SF), C-reactive protein (CRP) and erythropoietin (EPO) levels were measured. Results There was no significant difference between hepcidin level in peripheral blood and that in bone marrow (P=0.134). Stratified according to WHO 2008 subtypes, the hepcidin level in patients with refractory anemia with ringed sideroblasts (RARS) was the lowest [（105.40±5.13）ng/mL], and that in patients with refractory anemia with excess blasts (RAEB) was the highest [（335.71±25.16）ng/mL], and there were significant differences among groups (P=0.041). Stratified according to IPSS and WPSS, there were significant differences in hepcidin levels between low-risk group and high-risk group in two systems respectively (P<0.05 and P<0.01). The SF level and expression of GDF15 mRNA in WPSS highrisk group were significantly higher than those in WPSS low-risk group (P<0.05), while there was no significant difference between IPSS low-risk group and IPSS high-risk group (P>0.05). Stratified according to T lymphocyte subtype and polarization, the hepcidin level in CD4+ high-expression group was higher than that in normal expression group (P<0.05), but there was no significant difference in the hepcidin levels between CD19+ high-expression group and normal expression group (P=0.206), and the hepcidin level in Th1/Th2>70.6 group was higher than that in Th1/Th2≤70.6 group (P<0.001). Stepwise regression analysis revealed that liver iron concentration (LIC, measured by MRI T2*), instead of SF and cardiac T2*, was correlated with hepcidin (r=0.582, P<0.001). Conclusion Inflammation has a significant impact on hepcidin expression, and the activation and polarization of T lymphocytes may partially participate in the mechanism. T2*MRI outperformed SP in evaluation of iron overload in patients with MDS.

Key words: hepcidin, inflammation, magnetic resonance imaging T2*