CD26／二肽酰肽酶Ⅳ底物缓激肽在大鼠肺移植缺血再灌注损伤中的表达  

Expression of bradykinin as a substrate of CD26/DPP IV in rats ischemia/reperfusion injury following lung transplantation

作　　者：唐政[1] 王建军[1] 翟伟[1] 陈卓[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胸外科,武汉430022

出　　处：《中华器官移植杂志》2011年第7期426-429,共4页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金（30700767）;教育部归国留学人员基金（2008890）

摘　　要：目的研究CD26／二肽酰肽酶（DDP）Ⅳ底物缓激肽在大鼠肺移植缺血再灌注损伤中的表达。方法采用改进的三套管左侧大鼠原位肺移植方法构建模型，供、受者均为雄性SD大鼠。受鼠分为两组，每组18只。对照组受鼠接受用低钾右旋糖苷液灌洗并保存18h的供肺；实验组受鼠接受用含特异性不可逆DPPⅣ酶抑制剂（ABl92，终浓度25μmol／L）的低钾右旋糖苷液灌洗并保存18h的供肺。肺移植术后1d，获取移植肺，部分样本行蛋白质组学分析（二维凝胶电泳），并行质谱分析，鉴定与移植后缺血再灌注损伤相关的蛋白质；另外分别用免疫组化法和蛋白质印迹法检测缓激肽胆受体的表达。结果样本鉴定分析出差异蛋白质14个，其中对照组缓激肽前体（激肽原1）的表达高于实验组（P〈0．05）。蛋白质印迹证实，实验组缓激肽β2受体的表达低于对照组，差异有统计学意义（P〈（0．05）。免疫组化结果也证实，缓激肽β2受体在组织上呈分泌型表达，通常以呼吸道上皮细胞以及肺泡巨噬细胞周边染色较明显。对照组显色明显较深，缓激肽β2受体表达高于实验组。结论CD26／DDPⅣ酶活性抑制剂减轻大鼠肺移植术后早期缺血再灌注损伤的机制可能与其抑制激肽类物质的表达有关。Objective To investigate the expression of bradykinin as a substrate of CD26/DPP IV in rats with ischemia/reperfusion injury following lung transplantation （LTx）. Methods Thirty-six syngeneic male SD rats were randomly allocated into control group and experimental group （n = 18 each）, and 36 rats served as donors. In control group and experimental group, the lungs were flush- perfused and preserved with LPD and LPD ＋ CD26/DPP IV catalytic inhibitor （AB192） respectively, and LTx was performed 18 h after cold ischemia. Histopathological studies were also done on the same locus of lung specimens and staining for bradykinin. The different proteins were separated by means of immobilized PH gradient-based two-dimensional gel electrophoresis. The differential expression of bradykinin was compared by Western blotting. Results The expression of bradykinin in control group was significantly higher than in experimental group. As compared with experimental group, bradykinin expression was significantly up-regulated in control group （P 〈 0. 05 ）. Conclusion Inhibitor of CD26/DDP 1V enzymatic activity significantly ameliorated ischemia/reperfusion injury in the early stage after LTx, which is probably associated with inhibition of the protein expression of bradykinin.

关 键 词：肺移植 再灌注损伤 CD26/DPPⅣ酶 缓激肽 蛋白质组学 

分 类 号：R655.3[医药卫生—外科学]