端粒及端粒酶与再生障碍性贫血免疫抑制治疗疗效的关系  

The relationship of telomere and telomerase activity with outcome of aplastic anemia after immunesu pysessive therapy

作　　者：宋佳音[1] 邝丽萍[1] 王洋[1] 李勇华[1] 吴九龙[1] 张航[1] 李力[1] 王耀春[1] 蒋祖军[1] 肖扬[1] 

机构地区：[1]广州军区广州总医院血液科,广东510010

出　　处：《中华血液学杂志》2013年第9期771-776,共6页Chinese Journal of Hematology

基　　金：基金项目：国家自然科学基金（81101471/H1602）;全军医学科学技术研究“十二五”重点课题（Bws11J071）

摘　　要：目的观察再生障碍性贫血（AA）患者外周血单个核细胞（PBMNC）端粒长度及端粒酶活性与免疫抑制治疗（IST）疗效的关系，探讨AA发病机制及端粒长度对于评估IST疗效的意义。方法选取2010年9月至2013年3月71例AA患者，于初诊未接受治疗时留取外周血标本3ml。采用流式一荧光原位杂交法（flow—FISH）检测PBMNC端粒长度，采用端粒重复序列扩增一PCR．酶联免疫吸附测定法检测端粒酶活性。结果各组PBMNC端粒长度均随患者年龄增长而缩短（6—0．387，p=-0．001）。去掉年龄对PBMNC端粒长度影响，非重型AA（NSAA）组PBMNC端粒长度（30．957±4．502）与重型AA＋极重型AA组（29．510±5．911）比较差异无统计学意义（P=0．573），均短于正常对照组（51．086±10．844）（P值均〈0．01）。IST无效组患者初始PBMNC端粒长度（25．357±4．848）低于正常对照组（51．086±10．844），差异有统计学意义（P=0．005），而部分有效组（30．334±4．464）、完全有效组（32．808±4．685）与正常对照组比较差异均无统计学意义（P=0．517、P=0．254）。当AA患者PBMNC端粒长度低于界值点（29．21％）时，IST无效的可能性更大。PBMNC端粒酶活性NSAA组（0．234±0．175）、sAA＋VSAA组（0．324±0．178）均高于正常对照组（0．107±0．083），差异有统计学意义（P值均〈0．01）。结论部分AA患者PBMNC端粒长度较同龄正常人缩短、端粒酶活性相对增高，此类患者IST可能无效，应尽早调整治疗方案。端粒或可成为预测AA患者IST疗效的指标。Objective To observe the changes of telomere length and telomerase activity in patients with aplastic anemia （AA）, and relationship with immunosuppressive therapy （IST） efficacy, to explore the pathogenesis of AA and the role of telomere length in evaluating immunosuppressive therapy efficacy. Method 71 cases of AA patients between September 2010 and March 2013 were enrolled into this study. 3 ml peripheral blood specimens from this cohort of patients were collected to test the telomere length in peripheral blood mononuclear cell （PBMNC） with flow-FISH and detect telomerase activity with TRAP-PCR-ELISA method. Results Telomere length and age showed negative correlation （b=-0.387, P=- 0.001 ） in normal control, NSAA and SAA ＋ VSAA groups, telomere length became shorter with the growth of age, and normal control group telomere length decreased along with the age growth slightly greater than the other two groups （NSAA, SAA＋VSAA）. Besides the effect of age on telomere length, （30.957±4.502） （29.510±5.911 ） no significant difference was observed between NSAA and SAA＋VSAA groups （P=0.573）, and NSAA, SAA＋VSAA groups were significantly shorter than normal control group （51.086± 10.844） （P〈0.01）. Telomere length in NR group （25.357±4.848） was significantly lower than normal control group （51.086＋ 10.844） （P=0.005）, telomere length in CR （32.808＋4.685）/PR groups （30.334±4.464） compared with normal control group had no significant difference （P=-0.517, P=0.254）. Telomere length below 29.21% obviously decreased outcomes of IST. Telomerase activity had significant difference （Z2=20.385, P〈0.01 ）. The telomerase activity had no significant difference interms of age and gender in three groups, multiple comparison found that telomerase activities in SAA ＋ VSAA （0.324 ± 0.178） （P〈0.01）, and NSAA （0.234 ± 0.175）groups （P=-0.002） were significantly higher than normal control group （0.1074-0.083）. Conclusion Telomere le

关 键 词：贫血 再生障碍性 端粒 外周血单个核细胞 免疫抑制治疗 

分 类 号：R556.5[医药卫生—血液循环系统疾病]