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  

Effects of ZGDHu-1 on CD4^+ CD25^+ Regulatory T cells in Patients with Chronic B Cell Lymphocytic Leukemia in vitro.

作　　者：邱莲女[1] 周永列[1] 黄强[2] 胡惟孝[3] 

机构地区：[1]浙江省人民医院检验中心,杭州310014 [2]浙江省人民医院血液科,杭州310014 [3]浙江工业大学药学院

出　　处：《医学研究杂志》2011年第3期34-39,共6页Journal of Medical Research

基　　金：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)

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。Objective To 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. Methods Lymphocytes were isolated from PMBCs in patients with B -CLL and cocultured with or without ZGDHu -1. CD4＋ CD25 ＋/high CD127 low ,CD19 ＋ CD5 ＋ and viability rate, apoptosis, Fas,FasL,APO2.7, Bcl - 2 and Bax of CD4 ＋ CD25 ＋ Tregs were detected with flow cytometry, respectively. Results CD4 ＋ CD25 ＋/high CD127 low, CD19 ＋ CD5 ＋ in B - CLL were significantly higher than those of healthy controls. There was a positive correlation between CD4 ＋ CD25 ＋/high CD127 low and CD19 ＋ CD5 ＋ . After treatment of ZGDHu - 1 ;CD4 ＋ CD25 ＋/high CD127 low 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. Conclusion ZGDHu - 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.

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 

分 类 号：R392.4[医药卫生—免疫学]