过氧化物酶体增殖物激活型受体γ对原位肝移植胆道缺血-再灌注损伤的作用  

Effects of peroxisome proliferators activated receptor-gamma （PPAR-γ） on ischemia-reperfusion injury of bilr ducts after orthotopic liver transplantationwith

作　　者：裴红红[1] 黎一鸣[1] 张正良[1] 刘敏龙[1] 柏玲[1] 缪菲[1] 

机构地区：[1]西安交通大学医学院第二附属医院急诊科,西安710004

出　　处：《中华急诊医学杂志》2009年第3期277-280,共4页Chinese Journal of Emergency Medicine

基　　金：基金项目：陕西省科技发展计划资助项目（2005K14-G4）;西安市科技计划资助项目（GG06188）

摘　　要：目的探讨过氧化物酶体增殖物激活型受体γ（peroxisome proliferators activated receptorgamma, PPAR-γ）及配体罗格列列酮（rosiglitazone，Ros）对原位肝移植胆道缺血-再灌注损伤（Ischemia/reperfusion，I／R）的影响及其作用机制。方法42只SD大鼠随机分为假手术组（n=14），I／R组（n=14）和I／R＋Ros组（n=14）。通过制作大鼠肝脏原位缺血-再灌注模型，采用信号通路发现者基因芯片和大鼠细胞因子抗体芯片检测技术，检测胆道组织炎症反应发生的信号通路和相关的细胞因子的变化；并采用肝脏组织病理学评分和部分器官功能生化指标的检测，以观察大鼠缺血-再灌注损伤时肝脏组织的病理变化和部分器官生化指标的变化。采用SPSS 10．0软件进行统计学分析。实验中测得的数据以均数±标准差（x^-±s）表示，应用方差分析和Bonferroni检验，P〈0．05为差异具有统计学意义。结果I／R组中NF-κB样本基因表达水平均比假手术组和I／R＋Ros组升高两倍以上。使用大鼠细胞因子抗体芯片发现，I／R组中IL-1α，IL-1β以及TNF-α样本蛋白表达水平均比假手术组和I／R＋Ros组升高两倍以上。与I／R组相比，I／R＋Ros组中病理学评分明显下降（P〈0．05）；部分器官生化指标含量测定明显下降（P〈0．01）。结论PPAR-γ及配体罗格列酮对原位肝移植胆道缺血-再灌注损伤有保护作用，其机制与通过拮抗核因子-κB（NF-κB），抑制NF-κB表达，减少下游IL-1α，IL-1β以及TNF-α等炎性介质的释放有关。Objective To explore the effects and mechanism of peroxisome proliferators activated receptorgamma （PPAR-γ） and its ligand rosiglitazone on ischemia-reperfusion injury of the donor bile ducts. Method Forty-two SD rats were randomly divided into three groups with fourteen rats in each： the sham operation group （SO）, ischemia-repeffusion（I/R） group and I/R ＋ rosiglitazone group（I/R ＋ Ros）. The animal model of ischemia-reperfusion occurred in the orthotopically transplanted liver was used. The signal pathway of inflammatory response of bile ducts of the transplanted liver and the variations of associated cytokines were detected by the signal transduction pathway-finder gene array and cytokine antibody chips. The pathological changes and the biochemical markers of the donor liver were assessed by histopathological score and the estimation of the functional changes of some other organs. Data were analyzed by using SPSS version 10.0 software package. Statistical analysis was carried out by using one-way anova and Bonferroni test. Results Compared with the SO group and I/R ＋ Ros group, the expression of NF-κB gene of I/R group to more than two times, and the levels of IL-1α,IL-1β and TNF-α protein expressions in I/R group went up over double too. Compared with I/R group, the histopathological score and the biochemical markers of I/R ＋ Ros group were significantly lower （ P 〈 0.05, P 〈 0.01, respectively）. Conclusions PPAR-γ and its ligand msiglitazone have protective effects on ischemia-reperfusion injury to donor bile ducts. The mechanism may be attributed to decrease in the release of inflammatory mediators （IL-1α, IL-1β,TNF- α and so on） resulted from the down-expression of decreased due to NF-κB.

关 键 词：过氧化物酶体增殖体 缺血-再灌注损伤 原位肝移植 病理变化 生化指标 

分 类 号：R657.3[医药卫生—外科学]