中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (44): 8179-8182.doi: 10.3969/j.issn.1673-8225.2011.44.003

• 肝移植 liver transplantation • 上一篇    下一篇

肝移植后他克莫司血药浓度对外周血单个核细胞内HBV DNA的影响

吕立志，俞如胜，张小进，江  艺   

  1. 解放军南京军区福州总医院肝胆外科，福建省福州市  350025
  • 收稿日期:2011-05-22 修回日期:2011-07-15 出版日期:2011-10-29 发布日期:2011-10-29
  • 通讯作者: 江艺，博士，教授，解放军南京军区福州总医院肝胆外科，福建省福州市 350025 jiangyi63@126. com
  • 作者简介:吕立志★，男，1969年生，福建省晋江市人，汉族，1992年福建医科大学毕业，硕士，副主任医师，硕士生导师，主要从事肝移植、肝胆腹腔镜外科方面的研究。 llzhi69@126.com
  • 基金资助:

    南京军区医药卫生科研基金重点项目资助(06Z46)课题名称：树鼩乙型肝炎肝移植模型的建立有移植后乙型肝炎病毒动用学研究。

Effects of FK506 concentration on hepatitis B virus DNA in peripheral blood mononuclear cells after liver transplantation

Lü Li-zhi, Yu Ru-sheng, Zhang Xiao-jin, Jiang Yi   

  1. Department of Hepatobiliary Surgery, PLA Fuzhou General Hospital of Nanjing Military Area Command, Fuzhou 350025, Fujian Province, China
  • Received:2011-05-22 Revised:2011-07-15 Online:2011-10-29 Published:2011-10-29
  • Contact: Jiang Yi, Doctor, Professor, Department of Hepatobiliary Surgery, PLA Fuzhou General Hospital of Nanjing Military Area Command, Fuzhou 350025, Fujian Province, China
  • About author:Lü Li-zhi★, Master, Associate chief physician, Master’s supervisor, Department of Hepatobiliary Surgery, PLA Fuzhou General Hospital of Nanjing Military Area Command, Fuzhou 350025, Fujian Province, China llzhi69@126.com
  • Supported by:

    Scientific Research Foundation for Medical Science and Public Health of Nanjing Military Area Command of PLA, No.06Z46*

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摘要：

背景：肝移植后他克莫司等免疫抑制剂的长期应用导致机体细胞免疫功能降低，并有可能影响机体对乙肝病毒的清除。
目的：分析乙肝相关肝移植患者后不同浓度他克莫司对外周血单个核细胞中的HBV DNA含量的影响。
方法：纳入乙肝相关终末期肝病肝移植受者23例，根据移植后12周清晨空腹他克莫司血药浓度，分为高浓度组(≥ 10 μg/L) 9例和低浓度组(< 10 μg/L)14例，同时用荧光标记单克隆抗体结合流式细胞技术检测外周血T细胞亚群的百分比，用实时荧光定量PCR检测外周血单个核细胞内的HBV DNA。
结果与结论：用多元线性回归分析外周血单个核细胞内的HBV DNA含量与CD8+CD152+呈正相关，与CD8+CD28+呈负相关。高血药浓度他克莫司的患者外周血单个核细胞内的HBV DNA高于低浓度组，其改变与反映细胞免疫功能的指标CD8+CD152+和CD8+CD28+的变化有关。

关键词: 他克莫司, 肝移植, T细胞亚群, 外周血单个核细胞, 乙型肝炎病毒

Abstract:

BACKGROUND: The long term use of immunosuppressive agents in recipients of liver transplantation would result in decreased immune function and may affect the body's clearance of hepatitis B virus. 
OBJECTIVE: To analyze the relationship between FK506 concentration and hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMC) of the patients who underwent liver transplantation for HBV-related end-stage liver disease.
METHODS: Twenty-three patients with HBV-related end-stage liver disease who underwent liver transplantation from January 2009 to December 2009 were divided into FK506-high concentration (≥10 ng/mL) group (n=9) and FK506-low concentration group (< 10 ng/mL) group (n = 14) at 12 weeks after liver transplantation. At the same time, the copies of HBV DNA in PBMC and T-cell subsets (CD3+CD4+, CD3+CD8+, CD8+CD28+, CD8+CD152+) were determined respectively using real time fluorescent quantitative PCR combined with fluorescein-labelled monoclonal antibodies and flow cytometer.
RESULTS AND CONCLUSION: At 12 weeks after liver transplantation, the percentage of CD3+CD4+, CD3+CD8+, CD8+CD28+ in the FK506-high concentration group was significantly lower, and the percentage of CD8+CD152+ was significantly higher, compared with the FK506-low concentration group (P < 0.05). HBV DNA in the PBMC was significantly higher in the FK506-high concentration group than in the FK506-low concentration group (P < 0.05). Multiple linear regression of correlation of HBV DNA in PBMC and T-lymphocyte subsets after liver transplantation showed that HBV DNA was closely correlated with CD8+CD28+, CD8+CD152+. HBV DNA was significantly positively correlated with CD8+CD152+ and was negatively correlated with CD8+CD28+. Variance of FK506 concentration could suppress the expression of CD3+CD4+, CD3+CD8+, CD8+CD28+T-lymphocyte subsets and upregulate the expression of CD8+CD152+ T-lymphocyte subsets, which could inhibit cell immunity and affect HBV clearance in PBMC.

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