四嗪二甲酰胺对慢性B淋巴细胞白血病CD4+CD25+调节性T细胞体外作用的研究
投稿时间:2010-10-14    点此下载全文
引用本文:邱莲女,周永列,黄强,胡惟孝.四嗪二甲酰胺对慢性B淋巴细胞白血病CD4+CD25+调节性T细胞体外作用的研究[J].医学研究杂志,2011,40(3):34-39
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作者单位
邱莲女 浙江省人民医院检验中心 
周永列 浙江省人民医院检验中心 
黄强 血液科 
胡惟孝 浙江工业大学药学院 
基金项目:国家自然科学基金资助项目(30973568);浙江省医药卫生科学研究基金项目计划(2010KYA015);浙江省医学重点学科建设基金(07-010)
中文摘要:目的研究四嗪二甲酰胺(ZGDHu-1)对慢性B淋巴细胞白血病(chronic B cell lymphocytic leukemia,B-CLL)CD4+CD25+调节性T细胞(regulatory T cells,Tregs)的影响,初步探讨其对CD4+CD25+ Tregs的作用机制。方法B-CLL外周血淋巴细胞分离培养,流式细胞术检测ZGDHu-1作用前后CD4+CD25+/highCD127low、CD19+CD5+以及CD4+CD25+Tregs细胞活力、细胞凋亡、Fas、FasL、APO2.7及Bcl-2、Bax。结果B-CLL的CD4+CD25+/highCD127low、CD19+CD5+明显高于正常对照组,且CD4+CD25+/highCD127low与CD19+CD5+明显正相关。ZGDHu-1作用后,B-CLL的CD4+CD25+/highCD127low、CD19+CD5+明显降低,CD4+CD25+Tregs活力明显下降和凋亡明显升高;CD4+CD25-T细胞活力也有一定程度的下降,凋亡升高,但其凋亡明显低于CD4+CD25+Tregs。ZGDHu-1作用后,CD4+CD25+Tregs 的APO2.7明显增加,Bcl-2明显降低,Bax没有变化,而CD4+CD25-T细胞FasL明显增加。结论ZGDHu-1作用后B-CLL的CD4+CD25+Tregs明显下降,可能与Bcl-2/Bax比值降低,APO2.7表达增高,而促进B-CLL CD4+CD25+Tregs的凋亡有关。
中文关键词:四嗪二甲酰胺  慢性B淋巴细胞白血病  CD4+CD25+调节性T细胞  细胞凋亡  流式细胞术
 
Effects of ZGDHu-1 on CD4+CD25+ Regulatory T cells in Patients with Chronic B Cell Lymphocytic Leukemia in vitro
Abstract:ObjectiveTo investigate the effects of ZGDHu-1 on CD4+CD25+ regulatory T cells in patients with chronic B cell lymphocytic leukemia (B-CLL) to elucidate its effect mechanism on CD4+CD25+Tregs. MethodsLymphocytes were isolated from PMBCs in patients with B-CLL and cocultured with or without ZGDHu-1. CD4+CD25+/highCD127low,CD19+CD5+ and viability rate,apoptosis,Fas,FasL,APO2.7,Bcl-2 and Bax of CD4+CD25+Tregs were detected with flow cytometry,respectively.ResultsCD4+CD25+/highCD127low ,CD19+CD5+ in B-CLL were significantly higher than those of healthy controls. There was a positive correlation between CD4+CD25+/highCD127low and CD19+CD5+.After treatment of ZGDHu-1,CD4+CD25+/highCD127low and CD19+CD5+ decreased significantly, viability rate of CD4+CD25+Tregs decreased and apoptosis of CD4+CD25+Tregs increased significantly in B-CLL.At the same time, viability rate of CD4+CD25-T cells decreased to a certain extent,apoptosis of CD4+CD25-T cells increased and was significantly lower than that of CD4+CD25+Tregs. After treatment of ZGDHu-1, APO2.7 increased,Bcl-2 decreased significantly and bax didnot change in CD4+CD25+Tregs, FasL increased significantly in CD4+CD25-T cells. ConclusionZGDHu-1 could decrease CD4+CD25+Tregs significantly,which could be connected with promoting apoptosis of CD4+CD25+Tregs by decresing Bcl-2/Bax ratio and increasing APO2.7.
keywords:N,N′-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide  Chronic B cell lymphocytic leukemia  CD4+CD25+ regulatory T cells  Apoptosis  Flow cytometry
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