肝移植急性肺损伤患者围手术期血清细胞因子的比较蛋白组学分析

摘要

目的 分析肝移植围手术期急性肺损伤(ALI)的细胞因子表达特点,以期为筛选肝移植ALI的早期标志物和早期治疗靶点奠定基础.方法 乙型肝炎肝硬化行同种异体原位肝移植术后发生ALI男性患者4例,术前无肺、肾、脑等重要脏器异常,术中尿量、出血量、腹水量、血制品输入量、手术时间、无肝期时间及血管活性药物用量、利尿药使用情况及循环情况等差异无统计学意义.采集麻醉后、新肝3 h、新肝24 h的血清,利用RayBioR人抗体芯片试剂盒分析细胞因子的表达特点.结果 与健康者比较,肝移植ALI患者在麻醉后就已有部分细胞因子表达增强,包括白细胞介素(IL-3、IL-6、IL-12 p40、IL-12 p70)、单核细胞趋化蛋白2(MCP-2)、巨噬细胞集落刺激因子(M-CSF)、r-干扰素诱导单核因子(MIG)、巨噬细胞炎性蛋白-1a(MIP-1a)、可溶性肿瘤坏死因子受体I(sTNFR I),其中尤以sTNFR Ⅱ表达上调的幅度大,正常T细胞表达和分泌因子(RANTES)、血小板衍化生长因子-BB(PDGF-BB)表达明显下调.在新肝3 h时表达上调的细胞因子种类有所增加,其中尤以IL-12 p70、sTNFR I、sTNFRⅡ表达上调的幅度较大;RANTES、PDGF-BB、IL-1a表达明显下调.在新肝24 h时表达上调的细胞因子种类和程度大幅增加.与新肝3 h相比,新肝24 h嗜酸粒细胞选择性趋化因子(eotaxin)、IL-1a、IL-1β、IL-4、IL-15、MCP-2表达明显上调,IL-3、IL-6表达上调的幅度大,IL-2表达上调幅度最大.结论 在麻醉后、新肝3 h、新肝24 h分别有不同的炎症因子表达减弱或增强,且表达增强的幅度不同,某些因子的变化可能是重要的早期标志物和治疗靶点,提示需要进行大样本研究.%Objective To investigate the characteristics of serum cytokine expression in acute lung injury(ALI)patients in peri-operative stage of liver transplantation with the aim of setting the basis for screening the early markers and treatment targets of ALI.Methods Four male patients with ALI occurring in peri-operative stage of liver transplantation for hepatitis B liver cirrhosis,with no lung,renal,or brain abnormality,without difference inclinical findings(urine volumn,blood lOSS,ascites,amount of blood transfusion,operation time,anhepatic time,the use of vaso-active drugs,diuretics and condition of circulation)were included for study.Blood was taken after anesthesia,3 hours and 24 hours after new liver.RayBioR human antibody array was used to analyze the cytokine expression.Results Compared with healthy people,in the patients with ALI in peri-operative stage of liver transplantation,upregulation of some cytokines appeared as early as after anesthesia,including interleukins(IL-3,IL-6,IL-12 p40,IL-12 p70),monocyte chemoattractant protein-2(MCP-2),macrophage-colony stimulating factor(M-CSF),monokine induced by interferon-r(MIG),macro-phage inflammatory protein-1a(MIP-1a),soluble tumor necrosis factor receptor I(sTNFR I),especially sTNFR Ⅱ which showed even stronger expression,while normal T cells expression and secretory factor(RANTES)and platelet-derived growth factor-BB(PDGF-BB)showed downregulation in expression.Some more cytokines showed upregulation in expression at neohepatic 3 hours,especially IL-12 p70,sTNFR I,sTNFR Ⅱ showed upregulation,while RANTES,PDGF-BB and IL-1a showed downregulation in expression.The number of cytokines showing upregulation was significantly increased at neohepatic 24 hours.Compared with those at neohepatic 3 hours,eotaxin,IL-1a,IL-1β,IL-4,IL-15,MCP-2 showed significantly higher upregulation at neohepatic 24 hours,and among them IL-3 and IL-6 especially IL-2 showed even more upregulation in expression.Conclusion There are changes in expression of different kinds of cytokines in various extent before operation,at neohepatic 3 hours and neohepatic 24 hours.Some of them may be considered as important early markers and treatment targets.Further researches with large samples would be necessary to elucidate the clinical implication.