CAJ | 학술논문

目的探讨过氧化物酶体增殖物激活型受体γ(peroxisome proliferators activated receptor-gamma,PPAR-γ)及配体罗格列酮(rosiglitazone,Ros)对原位肝移植胆道缺血-再灌注损伤(Ischemia/reper-fusion,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).通过制作人鼠肝脏原位缺血-再灌注模型,采用信号通路发现者基因芯片和大鼠细胞冈予抗体芯片检测技术,榆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牛化指标的变化.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-кB样本基因表达水平均比假于术组和I/R+Ros组丌高两倍以上.使用大鼠细胞因子抗体芯片发现,I/R组中IL-Iα,IL-β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组巾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及配体罗格列嗣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-кB(NF-кB),抑制NF-кB表达,减少下游IL-Iα,IL-1β以及TNFα等炎性介质的释放有关.
목적 탐토과양화물매체증식물격활형수체γ(peroxisome proliferators activated receptor-gamma,PPAR-γ)급배체라격렬동(rosiglitazone,Ros)대원위간이식담도결혈-재관주손상(Ischemia/reper-fusion,I/R)적영향급기작용궤제.방법 42지SD대서수궤분위가수술조(n=14),I/R조(n=14)화I/R+Ros조(n=14).통과제작인서간장원위결혈-재관주모형,채용신호통로발현자기인심편화대서세포강여항체심편검측기술,유측담도조직염증반응발생적신호통로화상관적세포인자적변화;병채용간장조직병이학평분화부분기관공능생화지표적검측,이관찰대서결혈-재관주손상시간장조직적병리변화화부분기관우화지표적변화.채용SPSS 10.0연건진행통계학분석.실험중측득적수거이균수±표준차(x±s)표시.응용방차분석화Bonferroni검험,P＜0.05위차이구유통계학의의.결과 I/R조중NF-кB양본기인표체수평균비가우술조화I/R+Ros조기고량배이상.사용대서세포인자항체심편발현,I/R조중IL-Iα,IL-β이급TNF-α양본단백표체수평균비가수술조화I/R+Ros조승고량배이상.여I/R조상비,I/R+Ros조건병이학평분명현하강(P＜0.05);부분기관생화지표함량측정명현하강(P＜0.01).결론 PPAR-γ급배체라격렬사대원위간이식담도결혈-재관주손상유보호작용,기궤제여통과길항핵인자-кB(NF-кB),억제NF-кB표체,감소하유IL-Iα,IL-1β이급TNFα등염성개질적석방유관.
Objective To explore the effects and mechanism of peroxisome proliferators activated receptor-gamma(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-reperfusion(I/R)group and I/R+rosiglitazone group(I/R+Ros).The animal model of is-chemia-reperfusion occurred in the orthotopically transplanted liver was used.Tne signal pathway of iuflanunatory response of bile duets of the transplanted hver 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 car-ried out by using one-way anova and Bonferroni test.Results Compared with the SO group and I/R+Ros group.the expression of NF-кB gene of I/R group to more than two times,and the levels of IL-1α,IL-1β and TNF-α pro-tein 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).Con-clusions PPAR-γ and its ligand rosiglitazone 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-кB.