PARP-1激活和AIF易位在肠缺血再灌注损伤中的作用
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国家自然科学基金资助项目(30500134)


Intestinal injury after ischemia-reperfusion:role of PARP activation and AIF translocation
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    摘要:

    目的:研究大鼠肠缺血再灌注后肠损伤中是否存在聚腺苷二磷酸核糖聚合酶-1(PARP-1)激活和凋亡诱导因子(AIF)易位,并探索二者在肠缺血再灌注损伤中的作用-方法:通过阻断腹腔干和肠系膜上动脉30 min后,恢复血运,制作鼠肠缺血再灌注模型,分为肠缺血再灌注组(I/R),缺血再灌注前15min经静脉给PARP-1抑制剂3-AB组(Drug)和假手术组(Sham)-取肠组织分别作HE染色-聚腺苷二磷酸核糖(PAR)的免疫组化染色,TUNEL方法检测组织细胞凋亡情况,Western Blot检测凋亡早期信号PARP-1片段p85和凋亡诱导因子(AIF)的表达情况-结果:I/R组肠损伤程度-PAR阳性表达率-细胞凋亡率和凋亡早期信号PARP-1 p85片段-AIF表达程度均较Sham组显著增高(P < 0.05);应用PARP-1抑制剂后,Drug组上述指标均较I/R组显著降低(P < 0.05),但仍高于Sham组-结论:在大鼠肠缺血再灌注损伤中存在PARP-1激活和AIF易位两分子事件,并在肠缺血再灌注损伤中发挥重要作用;肠缺血再灌注前应用PARP-1抑制剂有肠保护效果-

    Abstract:

    Objective:To investigate the role of PARP activation and AIF translocation in intestinal injury after ischemia-reperfusion (I/R). Methods:The intestinal ischemia/reperfusion(I/R) model in rats was established by clamping both the celiac trunk and the superior mesenteric artery for 30 min,followed by reperfusion for 2h. The animals were assigned to different groups:I/R group,Drug group(3-AB,PARP inhibitor,30 mg/kg i.v.) and Sham group. The morphological changes of intestine,PARP-1 activation,apoptosis and the expression of PARP-1 cleavage p85 and AIF were detected by means of HE,immunohistochemical staining for poly(ADP-ribose),TUNEL and Western blot respectively. Results:In I/R group,the extent of intestinal injure and PARP-1 activation,the expression of PARP-1 cleavage p85,AIF and TUNEL positive-staining were elevated significantly. In Drug group,these variables were statistically lower than those in I/R group,but higher than those of Sham group. Conclusion:These findings indicate that PARP activation and AIF translocation contribute to intestinal injury after ischemia-reperfusion;PARP-1 inhibitor has the potential protection for intestinal I/R by inhibiting PARP-1 activation and preventing AIF translocation.

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邢〓莉,潘旭东,方〓纬,赵〓莉,刘光茂,李虎臣. PARP-1激活和AIF易位在肠缺血再灌注损伤中的作用[J].南京医科大学学报(自然科学版),2009,29(11):1489-

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  • 收稿日期:2009-08-01
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