Genescà Meritxell, Sola Anna, Miquel Rosa, Pi Felip, Xaus Carme, Alfaro Vicente, Hotter Georgina
Department of Medical Bioanalysis, Instituto de Investigaciones de Barcelona-Consejo Superior de Investigaciones Cientificas, Institut d' Investigacions Biomèdiques August Pi i Sunyer, Spain.
Am J Pathol. 2002 Nov;161(5):1839-47. doi: 10.1016/S0002-9440(10)64460-4.
The aim of this study was to evaluate whether xanthine and adenosine, substances modified proportionally to the duration of ischemia, can determine cell demise (apoptosis/necrosis) during intestinal ischemia/reperfusion (I/R) and to determine the role of nitric oxide (NO) during this process. The following experimental groups were studied: I, cold ischemia; I+X, effect of xanthine; I+T, effect of adenosine (blocking its receptor by theophylline); I+A, effect of excess adenosine; I+T+X, effect of xanthine alone, and I+T+ spermine NONOate (NONOs), I+A+NONOs, I+X+NONOs, role of NO. DNA fragmentation, xanthine/adenosine levels, caspase-3 activity, NO generation, and histological analysis were measured in tissue samples. The rats treated with xanthine or adenosine showed increased levels of caspase-3 activity and DNA fragmentation. In contrast, theophylline-treated rats showed decreased levels of DNA fragmentation and tended to show lower mean values of caspase-3 activity. Administration of xanthine or NONOs to theophylline-treated rats reversed these effects. The results of histological evaluation were in agreement with these previous results. In conclusion, the present study indicates that xanthine and adenosine induced an apoptotic response during cold ischemic preservation of rat small intestine. In particular, the action of adenosine on apoptotic events was mediated by NO. We consider that identification of the role of these factors may help to define the best conditions of tissue preservation before intestinal transplantation.
本研究的目的是评估黄嘌呤和腺苷（与缺血持续时间成比例变化的物质）是否能在肠缺血/再灌注（I/R）期间引发细胞死亡（凋亡/坏死），并确定一氧化氮（NO）在此过程中的作用。研究了以下实验组：I，冷缺血；I+X，黄嘌呤的作用；I+T，腺苷的作用（用茶碱阻断其受体）；I+A，过量腺苷的作用；I+T+X，单独黄嘌呤的作用，以及I+T+精胺NONOate（NONOs）、I+A+NONOs、I+X+NONOs，NO的作用。对组织样本测量了DNA片段化、黄嘌呤/腺苷水平、半胱天冬酶-3活性、NO生成及组织学分析。用黄嘌呤或腺苷处理的大鼠显示半胱天冬酶-3活性水平和DNA片段化增加。相反，用茶碱处理的大鼠显示DNA片段化水平降低，且半胱天冬酶-3活性平均值有降低趋势。对用茶碱处理的大鼠给予黄嘌呤或NONOs可逆转这些效应。组织学评估结果与这些先前结果一致。总之，本研究表明黄嘌呤和腺苷在大鼠小肠冷缺血保存期间诱导了凋亡反应。特别是，腺苷对凋亡事件的作用由NO介导。我们认为确定这些因素的作用可能有助于确定肠移植前组织保存的最佳条件。
