TNF对造血调控的影响及在高原红细胞增多症中的作用  

The effect of TNF on hematopoietic regulation and its role in high altitude polycythemia

作　　者：解友邦[1] 年蔚[2] 刘彦民[3] 高云梅[1] 石雪峰[4] 郗爱旗 Xie Youbang;Nian Wei;Liu Yanmin;Gao Yunmei;Shi Xuefeng;Xi Aiqi(Department of Hematology and Rheumatology,Qinghai Provincial People’s Hospital,Qinghai Province,Xi’ning810007,China;Department of Geriatrics,Qinghai Provincial People’s Hospital,Qinghai Province,Xi’ning810007,China;Department of Cardiovascular Intervention,Qinghai Provincial People’s Hospital,Qinghai Province,Xi’ning810007,China;Department of Respiratory and Intensive Care Unit,Qinghai Provincial People’s Hospital,Qinghai Province,Xi’ning810007,China;Department of Geriatrics,the Fourth People’s Hospital of Qinghai Province,QinghaiProvince,Xi’ning810000,China)

机构地区：[1]青海省人民医院血液风湿科,青海西宁810007 [2]青海省人民医院老年医学科,青海西宁810007 [3]青海省人民医院心血管介入科,青海西宁810007 [4]青海省人民医院呼吸与危重症医学科,青海西宁810007 [5]青海省第四人民医院老年医学科,青海西宁810000

出　　处：《中国医药导报》2020年第34期48-51,共4页China Medical Herald

基　　金：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]。

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。As one of the hematopoietic inhibitors,there are two main types of tumor necrosis factor(TNF)family:TNF-αand TNF-β.The effects of the two on stem cells and progenitor cells are different under different colony stimulating factor(CSF)stimulation.TNF-αactivates nuclear factor-κB(NF-κB)through its classical pathway,in which inhibitor-κbinding 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-αactivates Notch and NF-κB signal transduction pathways through TNFR2,and promotes HSC production under inflammatory signal transduction.TNF-βreceptor also named lymphotoxin-βreceptor(LTβR)which expresses in many hematopoietic tissues.TNF-βcan 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-βin 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-βmay play an important role in the erythropoiesis regulation of HAPC.

关 键 词：肿瘤坏死因子 造血调控 高原红细胞增多症 

分 类 号：R555[医药卫生—血液循环系统疾病]