摘要
目的:比较移植后患者外周血淋巴细胞不同基因表达时相与病理改变时相,探讨外周血淋巴细胞分子的表达与排斥反应的关系。方法:通过对9例脏器移植的观察,系统比较了移植器官的实时荧光定量PCR检测患者外周血淋巴细胞CD4、CD8、P56、P59编码基因表达时相改变、荧光差异显示技术检测差异基因表达时相及其与脏器功能、病理改变时相的关系。结果:免疫抑制剂不能完全阻断脏器移植排斥反应的发生;移植术后24 h内,9例患者荧光差异显示-PCR技术外周血淋巴细胞P59、酪氨酸磷酸酶的基因表达上调,24～48 h PKC-θ、CD4等基因表达上调;肾移植和心脏移植术后PKC-θ、MHC-Ⅱ、丝/苏氨酸激酶和酪氨酸磷酸酯酶及丝氨酸/苏氨酸激酶15、凝血因子VIII、干扰素诱导蛋白、HLA-DR-H基因较术前有3倍以上升高。P59编码基因表达水平于移植后24 h内保持基本平稳,此后持续负调表达直到第10天达低谷。P56和CD8基因于移植后72 h内表现为持续负调表达,此后正调表达并于第5天时达到移植后的第一个峰值。CD4编码基因于移植后24 h内首先表现为负调表达,此后开始正调表达并于48 h达到移植后的第一个峰值。结论:外周血淋巴细胞基因表达水平的监测可能有助于临床早期急性排斥反应的诊断和免疫抑制剂治疗效果的判断。
AIM： To investigate the time course of the gene expression after the organ transplantation, and try to identify the relationship of the gene and protein changes with the pathological progression and the immune rejection. METHODS： We systematically observed the gene expres- sion of CD4, CD8, P56, P59 by real-time PCR. The time courses of gene expression were analyzed by Fluorescent Differential Display after the organ transplantation. At the same time points, the clinical outcomes of the patients were followed up so that we could identify the relationship of the gene expression and the immune rejection. RESULTS： Immunosuppressive drugs could not prevent the transplantation rejection completely. P59 gene and tyrosine phosphatase genes started to express positively within 24 h after organ transplantation. Between 24-48 h, PKC-θ and CD4 gene expression levels increased. The expressions of PKC-θ, MHC-Ⅱ, serine/threonine kinase, tyrosine phosphatase, serine/threonine kinase 15, clotting factor Ⅷ, interferon gamma-inducible protein 16 and HLA-DR-H increased by three times compared to pre-transplantation in patients with kidney and heart transplantations. The expression of P59 gene remained stable within 24 h after transplantation, andthen decreased to the lowest level at day 10. P56 and CD8 levels were down-regulated within 72 h, and then up-regulated to the first peak at day 5. The expression of CD4 was also inhibited within 24 h, and then increased to the first peak at 48 h. CONCLUSION： The monitoring on the expressions of the proteins and genes on the peripheral lymphocytes may help to early find the clinical immune rejection after organ transplanta- tion and judge the efficiency of the anti-rejection drugs.
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2012年第10期1041-1045,1050,共6页
Chinese Journal of Cellular and Molecular Immunology
基金
首都医学发展科研基金(重点学科)(ZB199814)
关键词
脏器移植
外周血淋巴细胞
淋巴细胞基因表达
时相
organ transplantation
peripheral bloodlymphocytes
time-course of gene expres-sion
作者简介
同为第一作者:许秀芳(1969-),女,河南安阳人,副研究员,博士,Tel:010-64456462,E-mail:drxuxiufang@yahoo.com.cn;同为第一作者:辛毅(1968-),女,北京人,主管技师,本科,Tel:010-64456451,E-mail:xinyianzhen@163.com;Corresponding author:张兆光,E-mail:yb@yahoo.com.cn
