肝移植术后早期移植物功能不良的转录组学及临床因素分析  

Genomic profiles and clinical factors of early allograft dysfunction after liver transplantation

作　　者：庞春 李捷[1] 曹胜利[1] 温培豪[1] 王智慧[1] 胡博文[1] 史晓奕[1] 张嘉凯[1] 何玉婷[1] 郭文治[1] 张水军[1] Pang Chun;Li Jie;Cao Shengli;Wen Peihao;Wang Zhihui;Hu Bowen;Shi Xiaoyi;Zhang Jiakai;He Yuting;Guo Wenzhi;Zhang Shuijun(Department of Hepatobiliary&Pancreatic Surgery,First Affiliated Hospital,Zhengzhou University,Henan Organ Transplantation Medical Engineering Technology Center,Zhengzhou Key Laboratory of Hepatobiliary,Pancreatic&Organ Transplantation,Zhengzhou Key Laboratory of Organ Transplantation Technology&Application Engineering,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院肝胆胰外科,河南省器官移植医学工程技术中心,郑州市肝胆胰疾病与器官移植医学重点实验室,郑州市器官移植技术与应用工程重点实验室,450052

出　　处：《中华器官移植杂志》2020年第10期613-618,共6页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金项目(U1604282、81971881、81701946);河南省医学科技攻关计划省部共建项目(SBGJ2018002)。

摘　　要：目的分析影响脑死亡供者供肝移植术后受者早期移植物功能不良(early allograft dysfunction,EAD)的分子标志物及临床因素,建立将分子标志物和临床因素相结合的预测移植术后EAD的预警体系。方法回顾性分析2017年7月至2018年8月在郑州大学第一附属医院肝脏移植中心接受同种异体原位肝移植的87例成年受者的临床资料以及对应的供者临床信息。通过单因素分析,找出EAD的潜在危险因素,并进行Logistic回归分析以找出独立危险因素;并从中选取肝移植术后8例发生EAD和8例未发生EAD的组织标本,进行转录组测序,寻找与EAD相关信号通路。结果通过临床数据分析发现供者总胆红素、淋巴细胞以及受者术前总胆红素是脑死亡供者供肝移植术后受者EAD的独立危险因素。通过转录组测序发现EAD不良组与非EAD组之间有3857个显著差异的mRNA,其中1751个在发生EAD的供肝组织中表达上调,2106个下调。通过基因本体论和京都基因与基因组百科全书分析发现炎症与代谢相关的信号通路与移植术后EAD有关。结论早期移植物功能不良相关的炎症与代谢信号通路结合供者总胆红素、淋巴细胞以及受者术前总胆红素对预测肝移植受者早期移植物功能不良的发生具有潜在的诊断意义。Objective To establish an early warning system for predicting the post-transplantation occurrence of early allograft dysfunction(EAD)through molecular and clinical factors.Methods From July 2017 to August 2018,retrospective analysis was performed for clinical data of 87 adult recipients of orthotopic liver transplantation.The potential risk factors of EAD were identified by univariate analysis and the independent risk factors screened by logistic regression analysis.The tissue samples from 8 EAD cases and 8 non-EAD cases after liver transplantation were selected for transcriptome sequencing to search for the signal pathway related to EAD.Results Through clinical data analysis,total bilirubin,lymphocytes and preoperative bilirubin of donor were independent risk factors for EAD after liver transplantation.Transcriptome sequencing revealed 3857 significantly different mRNAs between EAD and non-EAD groups.And 1751 were up-regulated and 2106 down-regulated.GO/KEGG analysis indicated that the signaling pathways of inflammation and metabolism were correlated with EAD after transplantation.Conclusions Along with donor total bilirubin,lymphocyte and recipient total bilirubin,inflammatory and metabolic signaling pathways associated with EAD have potential diagnostic significance for predicting the occurrence of EAD.

关 键 词：肝移植 脑死亡 早期移植物功能不良 

分 类 号：R657.3[医药卫生—外科学]