sPD-1、sPD-L1水平变化在大鼠肝移植后急性排斥反应中诊断价值的初步探讨  

Preliminary investigation on the diagnostic values of sPD-1 and sPD-L1 changes in the acute rejection of rats after liver transplantation

作　　者：杨教文 陈涛 王政禄[3] 曹磊 涂金鹏[4] 郑虹[5] 高伟[4] 沈中阳 Yang Jiaowen;Chen Tao;Wang Zhenglu;Cao Lei;Tu Jinpeng;Zheng Hong;Gao Wei;Shen Zhongyang(The First Central Clinical School,Tianjin Medical University,Tianjin 300190,China;School of Medicine,Nankai University,Tianjin 300074,China;Biological Sample Resource Sharing Centre,Tianjin First Central Hospital,Tianjin 300192,China;Organ Transplantation Centre,Tianjin First Central Hospital,Tianjin 300192,China;Organ Transplantation Research Centre,Tianjin First Central Hospital,Tianjin 300070,China;Institute of Transplantation Medicine,Nankai University,Tianjin 300192,China)

机构地区：[1]天津医科大学第一中心临床医学院,天津300190 [2]南开大学医学院,天津300074 [3]天津市第一中心医院生物样本资源共享中心,天津300192 [4]天津市第一中心医院器官移植中心,天津300192 [5]天津市第一中心医院器官移植研究中心,天津300070 [6]南开大学移植医学研究院,天津300192

出　　处：《中华器官移植杂志》2025年第3期226-231,共6页Chinese Journal of Organ Transplantation

基　　金：国家重点研发计划(2020YFA0710802);天津市自然科学基金面上项目(22JCYBJC01230);天津市自然科学基金重点项目(21JCZRJC00160)。

摘　　要：目的通过大鼠肝移植模型探讨外周血中可溶性程序性细胞死亡蛋白1(soluble programmed cell death protein 1,sPD-1)、可溶性程序性细胞死亡蛋白配体1(soluble programmed cell death ligand 1,sPD-L1)对移植后急性排斥反应(acute rejection,AR)的潜在诊断价值。方法建立大鼠肝移植AR模型,设AR组(Lewis大鼠→BN大鼠)为实验组(6只),非AR组(BN大鼠→BN大鼠)为对照组(6只)。分别于术前1天及术后第1、3、7天采用酶联免疫吸附法检测外周血sPD-1、sPD-L1浓度,术后第7天采用免疫组织化学(immunohistochemistry,IHC)染色检测肝组织的PD-1、PD-L1表达水平。采用独立样本t检验和重复测量方差分析比较两组检测结果,Pearson相关分析sPD-1、sPD-L1浓度及其比值与排斥活动指数的相关性。结果术后第7天,实验组大鼠外周血的sPD-1浓度高于对照组[(218.59±36.88)比(164.95±15.82)ng/L],sPD-L1浓度低于对照组[(379.56±73.41)比(423.64±96.55)ng/L],sPD-1/sPD-L1比值高于对照组(0.44±0.12比0.36±0.07),组间比较,差异均有统计学意义(P值均<0.05)。相关分析显示,sPD-1浓度及sPD-1/sPD-L1比值与排斥活动指数呈正相关(r=0.680,P<0.05;r=0.795,P<0.01);sPD-L1浓度与排斥活动指数无相关性。IHC显示,实验组大鼠肝组织PD-1、PD-L1表达为阳性,对照组表达为阴性。结论sPD-1浓度及sPD-1/sPD-L1比值与大鼠肝移植后AR存在显著相关性。外周血sPD-1、sPD-1/sPD-L1比值可作为诊断肝移植AR的潜在标志物。ObjectiveTo investigate the potential diagnostic value of peripheral blood soluble programmed cell death protein 1(sPD-1)and soluble programmed cell death protein ligand 1(sPD-L1)in acute rejection(AR)following liver transplantation using a rat model.MethodsA rat liver transplantation AR model was established,with the AR group(Lewis→BN)set as the experimental group(n=6)and the non-AR group(BN→BN)as the control group(n=6).Peripheral blood sPD-1 and sPD-L1 concentrations were measured using enzyme-linked immunosorbent assay(ELISA)at 1 day before transplantation and at 1,3,and 7 days postoperatively.On postoperative day 7,the expression levels of PD-1 and PD-L1 in liver tissues were detected by immunohistochemistry(IHC).Independent samples t-test and repeated measures ANOVA were used to compare the results between the two groups.Pearson correlation analysis was conducted to evaluate the relationship between sPD-1,sPD-L1,the sPD-1/sPD-L1 ratio,and the rejection activity index.ResultsOn postoperative day 7,the experimental group exhibited significantly higher peripheral sPD-1 levels(218.59±36.88 vs.164.95±15.82 ng/L)and a higher sPD-1/sPD-L1 ratio(0.44±0.12 vs.0.36±0.07),but lower sPD-L1 levels(379.56±73.41 vs.423.64±96.55 ng/L)compared to the control group(all P<0.05).Correlation analysis revealed a significant positive correlation between sPD-1 levels and the rejection activity index(r=0.680,P<0.05),as well as between the sPD-1/sPD-L1 ratio and the rejection activity index(r=0.795,P<0.01),while no correlation was observed between sPD-L1 levels and the rejection activity index.IHC demonstrated positive PD-1 and PD-L1 expression in the liver tissues of the experimental group,whereas the control group showed negative expression.ConclusionPeripheral blood sPD-1 levels and the sPD-1/sPD-L1 ratio are significantly associated with AR after liver transplantation in rats,suggesting their potential as biomarkers for diagnosing AR in liver transplant recipients.

关 键 词：大鼠 肝移植 急性排斥反应 可溶性程序性细胞死亡蛋白1 可溶性程序性细胞死亡蛋白配体1 

分 类 号：R657.3[医药卫生—外科学]