重型再生障碍性贫血的研究进展
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摘要
重型再生障碍性贫血(SAA)是由多种病因导致的骨髓造血功能衰竭,以造血干细胞损伤、造血微环境异常及免疫功能紊乱导致严重的贫血、感染、出血为临床表现的重度骨髓衰竭性疾病。SAA发病机制复杂,至今尚未完全明了。随着医疗水平的提高,人们对于SAA的认识已从宏观微观有了质的飞跃。目前对SAA病因的研究热点主要集中在T细胞亚群的异常、负性调控因子水平的改变、细胞凋亡等,现就这些方面的研究进行综述。
severe aplastic anemia(SAA) is a bone marrow function by a variety of causes of failure to hematopoietic stem cell damage, hematopoietic microenvironment disorders and immune dysfunction leads to severe anemia, infection, bleeding clinical manifestations severe bone marrow failure diseases. SAA pathogenesis of complex, has not yet fully understood. With the improvement of medical standards, people's understanding from the macro and micro SAA has been a qualitative leap. At present the cause of the SAA research focus mainly concentrated in the abnormal T cell subsets, a negative regulator of level changes and apoptosis, are reviewed on research in these areas.
severe aplastic anemia(SAA) is a bone marrow function by a variety of causes of failure to hematopoietic stem cell damage, hematopoietic microenvironment disorders and immune dysfunction leads to severe anemia, infection, bleeding clinical manifestations severe bone marrow failure diseases. SAA pathogenesis of complex, has not yet fully understood. With the improvement of medical standards, people's understanding from the macro and micro SAA has been a qualitative leap. At present the cause of the SAA research focus mainly concentrated in the abnormal T cell subsets, a negative regulator of level changes and apoptosis, are reviewed on research in these areas.
引文
[1]吴迪炯,周郁鸿,沈一平.慢性再生障碍性贫血中医认识及优势进展[J].中华中医药学刊,2012,30(3):500-2.
[2]Guo Y,Kartawinata M,Li J,et al.Inherited bone marrow failure associated with germline mutation of ACD,the gene encoding telomere protein TPP1[J].Blood,2014,124(18):2767-74.
[3]郭卫卫,李君梅.再生障碍性贫血机制的研究进展[J].中国医学工程,2011,19(1):165-6.
[4]Weiss DJ.New insights into the physiology and treatment of acquired myelodysplastic syndromes and aplasticpancytopenia[J].Vet Clin North Am Small Anim Pract,2003(6):1317-34.
[5]杨蓉,谢晓恬.再生障碍性贫血免疫学发病机制的研究进展[J].中国小儿血液与肿瘤杂志,2009,14(1):42-5.
[6]Chalayer E,French M,Cathebras P.Aplastic anemia as a feature of systemic lupus erythematosus:a case report and literature review[J].Rheumatol Int,2015,35(6):1073-82.
[7]Sa Q,Woodward J,Suzuki Y.IL-2 produced by CD8+immune T cells can augment their IFN-γproductionindependently from their proliferation in the secondary response to an intracellular pathogen[J].J Immunol,2013,190(5):2199-207.
[8]Liu Z,Liu JQ,Talebian F,et al.IL-27 enhances the survival of tumor antigen-specific CD8+T cellsand programs them into IL-10-producing,memory precursor-like effector cells[J].Eur J Immunol,2013,43(2):468-79.
[9]翟春燕,魏武,纪爱芳,等.马钱子碱对再生障碍性贫血患者T细胞分泌功能和增殖能力的影响[J].中国实验血液学杂志,2011,19(2):435-8.
[10]Keckler MS.Dodging the CTL response:viral evasion of Fas andgranzyme induced apoptosis[J].Front Biosci,2007,12(7):725-32.
[11]冯乐,付蓉,王化泉.重型再生障碍性贫血患者CD8+效应T细胞损伤骨髓造血途径的研究[J].中华血液学杂志,2011,32(9):597-601.
[12]Liu CY,Fu R,Wang J,et al.Expression of lymphokines in CD8(+)HLA-DR(+)T lymphocytesof patients with severe aplastic anemia[J].Chin J Med,2012,92(18):1240-3.
[13]刘宝山,顾民华,王兴丽,等.慢性再生障碍性贫血辨证分型与Fas/Fas L蛋白表达相关性研究[J].天津中医药,2009,26(4):280-3.
[14]楚玉洁,蒋军广,谭伟丽,等.凋亡相关基因Fas/Fasl在非小细胞肺癌中的表达及临床意义[J].中国老年学杂志,2014,4(8):2083-5.
[15]Nabhani S,Hnscheid A,Oommen PT,et al.A novelhomozygous Fas ligand mutation leads to early protein truncation,abrogation of death receptor and reverse signaling anda severe form of the autoimmune lymphoproliferative syndrome[J].Clin Immunol,2014,28(2):231-7.
[16]Luther WA,Nissen C,Wodnar FA.Intracellular Fas ligand is elevated in T lymphocytes in severe aplastic anaemia[J].Br J Haematol,2001,114(4):884-90.
[17]胡明辉,周永明,文伟,等.健脾补肾活血方对再生障碍性贫血患者骨髓造血细胞Fas及Fas L影响[J].福建中医药学报,2007,38(2):9-10.
[18]Liu CY,Fu R,Wang HQ,et al.Fas/Fas L in the immune pathogenesis of severe aplastic anemia[J].Genet Molecul Res,2014,13(2):4083-8.
[19]王良妥,张湘兰,谭日标.T细胞亚群在再生障碍性贫血外周血的表达及临床意义[J].海南医学杂志,2011,22(14):93-5.
[20]G?man A,G?man G,Bold A.Acquired aplastic anemia:correlation between etiology,pathophysiology,bone marrow histology and prognosis factors[J].Rom J Morphol Embryol,2009,50(4):669-74.
[21]何淑娅,蒋能刚,曾婷婷,等.免疫抑制治疗对再生障碍性贫血患者外周血淋巴细胞胞浆内TNF-α/IFN-γ表达的影响[J].中国实验血液学志,2011,19(3):689-91.
[22]Dubey S,Shukla P,Nityanand S.Expression of interferon-gamma andtumor necrosis factor-alpha in bone marrow Tcells and their levels inbone marrow plasma in patients with aplastic anemia[J].Ann Hematol,2005,84(9):572-7.
[23]刘晓,付蓉,王珺,等.肿瘤坏死因子-β对重型再生障碍性贫血患者效应T细胞损伤骨髓造血的影响[J].中国免疫学杂志,2012,5(28):544-5.
[24]Li JP,Zheng CL,Han ZC.Abnormal immunity and stem/progenitor cells in acquired aplastic anemia[J].Crit Rev Oncol Hematol,2010,75(2):79-93.
[25]Brinkmeier H,Ohlendieck K.Chaperoning heat shock proteins:proteomic analysis and relevance for normal anddystrophin-deficient muscle[J].Proteomics Clin Appl,2014,8(11/12):875-95.
[26]Gabai VL,Meng L,Kim G,et al.Heat shock transcription factor Hsf1 is involved intumor progression via regulation of hypoxiainducible factor 1 and RNA-binding protein Hu R[J].Mol Cell Biol,2012,32(5):929-40.
[27]Rawat P,Mitra D.Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways[J].Nucleic Acids Res,2011,39(14):5879-92.
[28]Takii R,Inouye S,Fujimoto M,et al.Heat shock transcription factor1 inhibits expression of IL-6 through activating transcription factor3[J].J Immunol,2010,184(2):1041-8.
[29]Eden W,Anherwijnen M,Wagenaar J,et al.Van der Zee R.stress proteins are used by the immunesystem for cognate interactions with anti-inflammatory regulatory T cells[J].FEBS Lett,2013,587(13):1951-8.
[30]肖卫民,鄂顺梅,刘瑛,等.热休克因子1调控的细胞凋亡相关基因的筛选与鉴定[J].研究论文摘要,2012,11(8):111-3.
[31]Shunmei E,Zhao YB,Huang YH,et al.Heat shock factor 1 is a transcription factor of Fas gene[J].Mol Cells,2010,29(5):527-31.
[32]欧阳华伟,谭军,黎高峰,等.热休克转录因子1对肿瘤坏死因子α的转录调控作用及机制[J].实用预防医学,2013,20(7):108-10.
[33]杨小艳,刘宝山.补肾化痰活血法对慢性再障患者疗效的临床观察[J].辽宁中医杂志,2011,38(1):23-4.
[34]丰纪明.中西医结合治疗慢性再生障碍性贫血临床分析[J].黔南民族医专学报,2014,27(3):177-9.
[35]朱玲玲,朱晓光.加味八珍汤对慢性再生障碍性贫血患者骨髓液中成纤维细胞生长因子-1的影响[J].广州中医药大学学报,2015,32(5):830-3.
[2]Guo Y,Kartawinata M,Li J,et al.Inherited bone marrow failure associated with germline mutation of ACD,the gene encoding telomere protein TPP1[J].Blood,2014,124(18):2767-74.
[3]郭卫卫,李君梅.再生障碍性贫血机制的研究进展[J].中国医学工程,2011,19(1):165-6.
[4]Weiss DJ.New insights into the physiology and treatment of acquired myelodysplastic syndromes and aplasticpancytopenia[J].Vet Clin North Am Small Anim Pract,2003(6):1317-34.
[5]杨蓉,谢晓恬.再生障碍性贫血免疫学发病机制的研究进展[J].中国小儿血液与肿瘤杂志,2009,14(1):42-5.
[6]Chalayer E,French M,Cathebras P.Aplastic anemia as a feature of systemic lupus erythematosus:a case report and literature review[J].Rheumatol Int,2015,35(6):1073-82.
[7]Sa Q,Woodward J,Suzuki Y.IL-2 produced by CD8+immune T cells can augment their IFN-γproductionindependently from their proliferation in the secondary response to an intracellular pathogen[J].J Immunol,2013,190(5):2199-207.
[8]Liu Z,Liu JQ,Talebian F,et al.IL-27 enhances the survival of tumor antigen-specific CD8+T cellsand programs them into IL-10-producing,memory precursor-like effector cells[J].Eur J Immunol,2013,43(2):468-79.
[9]翟春燕,魏武,纪爱芳,等.马钱子碱对再生障碍性贫血患者T细胞分泌功能和增殖能力的影响[J].中国实验血液学杂志,2011,19(2):435-8.
[10]Keckler MS.Dodging the CTL response:viral evasion of Fas andgranzyme induced apoptosis[J].Front Biosci,2007,12(7):725-32.
[11]冯乐,付蓉,王化泉.重型再生障碍性贫血患者CD8+效应T细胞损伤骨髓造血途径的研究[J].中华血液学杂志,2011,32(9):597-601.
[12]Liu CY,Fu R,Wang J,et al.Expression of lymphokines in CD8(+)HLA-DR(+)T lymphocytesof patients with severe aplastic anemia[J].Chin J Med,2012,92(18):1240-3.
[13]刘宝山,顾民华,王兴丽,等.慢性再生障碍性贫血辨证分型与Fas/Fas L蛋白表达相关性研究[J].天津中医药,2009,26(4):280-3.
[14]楚玉洁,蒋军广,谭伟丽,等.凋亡相关基因Fas/Fasl在非小细胞肺癌中的表达及临床意义[J].中国老年学杂志,2014,4(8):2083-5.
[15]Nabhani S,Hnscheid A,Oommen PT,et al.A novelhomozygous Fas ligand mutation leads to early protein truncation,abrogation of death receptor and reverse signaling anda severe form of the autoimmune lymphoproliferative syndrome[J].Clin Immunol,2014,28(2):231-7.
[16]Luther WA,Nissen C,Wodnar FA.Intracellular Fas ligand is elevated in T lymphocytes in severe aplastic anaemia[J].Br J Haematol,2001,114(4):884-90.
[17]胡明辉,周永明,文伟,等.健脾补肾活血方对再生障碍性贫血患者骨髓造血细胞Fas及Fas L影响[J].福建中医药学报,2007,38(2):9-10.
[18]Liu CY,Fu R,Wang HQ,et al.Fas/Fas L in the immune pathogenesis of severe aplastic anemia[J].Genet Molecul Res,2014,13(2):4083-8.
[19]王良妥,张湘兰,谭日标.T细胞亚群在再生障碍性贫血外周血的表达及临床意义[J].海南医学杂志,2011,22(14):93-5.
[20]G?man A,G?man G,Bold A.Acquired aplastic anemia:correlation between etiology,pathophysiology,bone marrow histology and prognosis factors[J].Rom J Morphol Embryol,2009,50(4):669-74.
[21]何淑娅,蒋能刚,曾婷婷,等.免疫抑制治疗对再生障碍性贫血患者外周血淋巴细胞胞浆内TNF-α/IFN-γ表达的影响[J].中国实验血液学志,2011,19(3):689-91.
[22]Dubey S,Shukla P,Nityanand S.Expression of interferon-gamma andtumor necrosis factor-alpha in bone marrow Tcells and their levels inbone marrow plasma in patients with aplastic anemia[J].Ann Hematol,2005,84(9):572-7.
[23]刘晓,付蓉,王珺,等.肿瘤坏死因子-β对重型再生障碍性贫血患者效应T细胞损伤骨髓造血的影响[J].中国免疫学杂志,2012,5(28):544-5.
[24]Li JP,Zheng CL,Han ZC.Abnormal immunity and stem/progenitor cells in acquired aplastic anemia[J].Crit Rev Oncol Hematol,2010,75(2):79-93.
[25]Brinkmeier H,Ohlendieck K.Chaperoning heat shock proteins:proteomic analysis and relevance for normal anddystrophin-deficient muscle[J].Proteomics Clin Appl,2014,8(11/12):875-95.
[26]Gabai VL,Meng L,Kim G,et al.Heat shock transcription factor Hsf1 is involved intumor progression via regulation of hypoxiainducible factor 1 and RNA-binding protein Hu R[J].Mol Cell Biol,2012,32(5):929-40.
[27]Rawat P,Mitra D.Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways[J].Nucleic Acids Res,2011,39(14):5879-92.
[28]Takii R,Inouye S,Fujimoto M,et al.Heat shock transcription factor1 inhibits expression of IL-6 through activating transcription factor3[J].J Immunol,2010,184(2):1041-8.
[29]Eden W,Anherwijnen M,Wagenaar J,et al.Van der Zee R.stress proteins are used by the immunesystem for cognate interactions with anti-inflammatory regulatory T cells[J].FEBS Lett,2013,587(13):1951-8.
[30]肖卫民,鄂顺梅,刘瑛,等.热休克因子1调控的细胞凋亡相关基因的筛选与鉴定[J].研究论文摘要,2012,11(8):111-3.
[31]Shunmei E,Zhao YB,Huang YH,et al.Heat shock factor 1 is a transcription factor of Fas gene[J].Mol Cells,2010,29(5):527-31.
[32]欧阳华伟,谭军,黎高峰,等.热休克转录因子1对肿瘤坏死因子α的转录调控作用及机制[J].实用预防医学,2013,20(7):108-10.
[33]杨小艳,刘宝山.补肾化痰活血法对慢性再障患者疗效的临床观察[J].辽宁中医杂志,2011,38(1):23-4.
[34]丰纪明.中西医结合治疗慢性再生障碍性贫血临床分析[J].黔南民族医专学报,2014,27(3):177-9.
[35]朱玲玲,朱晓光.加味八珍汤对慢性再生障碍性贫血患者骨髓液中成纤维细胞生长因子-1的影响[J].广州中医药大学学报,2015,32(5):830-3.