TNF对造血调控的影响及在高原红细胞增多症中的作用

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摘要作为造血抑制因子之一的肿瘤坏死因子（TNF）家族主要有TNF-α和TNF-β两种，两者对干细胞和祖细胞的作用在不同的集落刺激因子（CSF）刺激下作用不同。TNF-α通过其经典途径激活核因子κB（NF-κB），其中NF-κB抑制剂（IκB）被磷酸化后释放NF-κB二聚体，易位至细胞核以结合特异性NF-κB DNA结合位点以激活基因表达，正调节参与造血干细胞（HSC）和祖细胞维持和稳态的基因转录，TNF-α通过肿瘤坏死因子受体2（TNFR2）激活Notch和NF-κB信号传导途径，在炎症信号传导下促进HSC产生。TNF-β受体，即淋巴毒素-β受体（LTβR）表达于许多造血组织，TNF-β可以激活NF-κB信号通路产生一系列生物学效应，LTβR信号传导以细胞类型限制的方式导致NF-κB活化，而高原红细胞增多症（HAPC）骨髓上清中的TNF-β水平明显升高，同时骨髓CD71+细胞存在PI3K/Akt信号通路的激活，提示TNF-β在HAPC红系造血调控中可能发挥重要作用。

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	解友邦1 年蔚2 刘彦民3 高云梅1 石雪峰4 郗爱旗5

关键词 ：肿瘤坏死因子, 造血调控, 高原红细胞增多症

Abstract：As one of the hematopoietic inhibitors, there are two main types of tumor necrosis factor (TNF) family: TNF-α and TNF-β. The effects of the two on stem cells and progenitor cells are different under different colony stimulating factor (CSF) stimulation. TNF-α activates nuclear factor-κB (NF-κB) through its classical pathway, in which inhibitor-κ binding protein (IκB) is phosphorylated and releases NF-κB dimer, which translocates to the nucleus to bind specific NF-κB DNA. The binding site activates gene expression and positively regulates gene transcription involved in the maintenance and homeostasis of hematopoietic stem cells (HSC) and progenitor cells. TNF-α activates Notch and NF-κB signal transduction pathways through TNFR2, and promotes HSC production under inflammatory signal transduction. TNF-β receptor also named lymphotoxin-β receptor (LTβR) which expresses in many hematopoietic tissues. TNF-β can activate the NF-κB signaling pathway to produce a series of biological effects. LTβR signaling leads to NF-κB activation in a cell type-restricted manner. The level of TNF-β in bone marrow supernatant of high altitude polycythemia (HAPC) was significantly increased. There is PI3K/Akt signaling pathway activation in bone marrow CD71+ cells of HAPC. The above suggests that TNF-β may play an important role in the erythropoiesis regulation of HAPC.

Key words： Tumor necrosis factor Hematopoietic regulation High altitude polycythemia

基金资助:国家自然科学基金资助项目（81960027）；
青海省重点研发和重点项目（2018-SF-114）；
青海省卫计委指导项目（2018-wjzdx-21）；
青海省卫生骨干人才项目[青卫科办〔2018〕5号]。

通讯作者: 郗爱旗（1964.1-），男，主任医师；研究方向：老年及高原病的基础及临床研究。

作者简介: 解友邦（1980.6-），男，博士，副主任医师；研究方向：血液及高原病的基础及临床研究。

引用本文:

解友邦1 年蔚2 刘彦民3 高云梅1 石雪峰4 郗爱旗5. TNF对造血调控的影响及在高原红细胞增多症中的作用[J]. 中国医药导报, 2020, 17(34): 48-51.
Xie Youbang1 Nian Wei2 Liu Yanmin3 Gao Yunmei1 Shi Xuefeng4 Xi Aiqi5. The effect of TNF on hematopoietic regulation and its role in high altitude polycythemia. 中国医药导报, 2020, 17(34): 48-51.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2020/V17/I34/48

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