乌司他丁干预减体积肝移植模型大鼠的肝脏代谢  

Ulinastatin improves rat liver metabolism after reduced-size liver transplantation

作　　者：高红强 刘静 李志强 王海雷 赵雄齐 张升宁 冉江华 李立 Gao Hongqiang;Liu Jing;Li Zhiqiang;Wang Hailei;Zhao Xiongqi;Zhang Shengning;Ran Jianghua;Li Li(Department of Hepato-Biliary-Pancreatic Surgery,Calmette Hospital&the First Hospital of Kunming,Kunming Medical University,Kunming 650011,Yunnan Province,China)

机构地区：[1]昆明医科大学附属甘美医院昆明市第一人民医院肝胆胰外科,云南省昆明市650011

出　　处：《中国组织工程研究》2019年第3期435-440,共6页Chinese Journal of Tissue Engineering Research

基　　金：云南省应用基础研究计划(2013FZ218);项目负责人:刘静;云南省卫生科技计划(2014NS199);项目负责人:李立~~

摘　　要：背景:乌司他丁在肝切除、肝移植后抗炎、脏器保护、改善微循环等方面的作用已经有大量的研究,然而其作用的microRNA调控机制尚未见报道。目的:观察模型大鼠减体积肝移植后乌司他丁干预microRNA及蛋白组学的变化,并在差异表达的microRNAs和蛋白中预测microRNA对其靶向蛋白的调控,为乌司他丁的临床应用提供更深入的理论依据。方法:以Kamada的双袖套法为基础建立40%减体积肝移植模型大鼠,实验分2组:实验组在肝移植后0,12,24,36,48 h经腹腔注入乌司他丁(100 U/g);对照组在同样时间点注入生理盐水2 mL。在移植后24,48 h取2组大鼠肝脏分别行microRNA芯片检查及蛋白质质谱分析。将二者的结果输入mirTarBase软件进行靶基因预测。结果与结论:①与对照组相比,实验组表达差异超过2倍的mi RNAs有19个,蛋白丰度表达差异超过1.5倍的蛋白有17个,靶基因预测发现一组具有强力证据推荐的microRNA目标蛋白的调控通道:rno-mi R-181a-5p和Gpx1;②结果表明,模型大鼠减体积肝移植后,乌司他丁的使用,改变了rno-mi R-181a-5p的表达,rno-mi R-181a-5p通过调控Gpx1表达来改善模型大鼠减体积肝移植术后肝脏的代谢,这可能是乌司他丁作用机制之一。BACKGROUND:Effects of ulinastatin in anti-inflammatory,viscera protection and improving microcirculation after liver resection or liver transplantation have been widely researched.However,the role of microRNA regulation mechanism of ulinastatin has not yet been reported.OBJECTIVE:To discover the variation of microRNA expression profile and the change of proteomics in rats after reduced-size liver transplantation using ulinastatin,and to investigate if there is a lien between differentially expressed miroRNAs and proteins,so as to provide an in-depth theoretical evidence for clinical application of ulinastatin.METHODS:Rat models of reduced-size liver transplantation were established using the Kamada double cuff method and then divided into two groups.Rats in the experimental and control groups were given intraperitoneal injection of ulinastatin(100 U/g)and normal saline(2 mL)respectively at 0,12,24,36,and 48 hours after surgery.miroRNA chip and proteomic analysis were performed at 24 and 48 hours after transplantation.Then results were then imported into mirTarBase software for target prediction.RESULTS AND CONCLUSION:Compared with the control group,in the experimental group,there were 19 differentially expressed(>two-fold)proteins and 17 differentially expressed(>1.5 fold)proteins in rats.A miRNA regulation channel:miR-181-a-5p and Gpx1 were found.To conclude,after reduced-size liver transplantation in rats,use of ulinastatin alters miR-181-a-5p expression,which improves liver metabolism through regulating Gpx1 expression.This may be one mechanism of action of ulinastatin.

关 键 词：乌司他丁 microRNAs芯片 蛋白质质谱 miR-181-a-5p 大鼠减体积肝移植 缺血再灌注损伤 组织构建 微RNAS 质谱法 肝移植 再灌注损伤 组织工程 

分 类 号：R446[医药卫生—诊断学]