Ilhan Huseyin, Alatas Ozkan, Tokar Baran, çOlak Omer, Paşaoĝlu Ozgül, Koku Naim
Department of Pediatric Surgery, Osmangazi University, School of Medicine, Eskisehir, Turkey.
J Pediatr Surg. 2003 Nov;38(11):1591-5. doi: 10.1016/s0022-3468(03)00568-2.
The aim of this study was to evaluate the effect of allopurinol, methylene blue, and a monoclonal antibody to the adhesion molecule ICAM-1 in intestinal ischemia and reperfusion injury.
The rats were divided into 5 groups. CG (n = 8) was untreated controls, SISG (n = 11) received sterile isotonic saline solution, ICAMG (n = 12) received a monoclonal antibody to rat ICAM-1, ALLOG (n = 12) received allopurinol, and MBG (n = 14) received methylene blue. Intestinal ischemia was performed for 60 minutes followed by 60 minutes of reperfusion. The agents were injected 10 minutes before the reperfusion to animals. After 60 minutes of reperfusion, the plasma samples for myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-alpha) and uric acid levels, and the intestinal biopsies of ileum and jejunum for histopathologic examination were taken.
The mucosal damage was attenuated, and TNF-alpha level significantly decreased in ALLOG and ICAMG compared with SISG. The MPO activity was the lowest in ICAMG, and uric acid level was significantly decreased in ALLOG compared with the other groups. Methylene blue decreased TNF-alpha response to reperfusion injury but significantly increased the grade of the mucosal damage and the MPO activity.
This study shows that prereperfusion application of allopurinol and monoclonal antibody to the adhesion molecule ICAM-1 may attenuate the damage caused by intestinal ischemia and reperfusion, but the different time-points for application, the effects observed in the different ischemia and reperfusion durations, and the long-term results also should be investigated in the same experimental model before the final conclusion. Methylene blue was not effective to prevent or attenuate the intestinal tissue injury, but because this was the first study examining the effect of methylene blue on intestinal reperfusion injury, further studies with the different doses, ischemic duration, and application times will be needed.
本研究旨在评估别嘌醇、亚甲蓝以及一种针对黏附分子细胞间黏附分子-1（ICAM-1）的单克隆抗体在肠道缺血再灌注损伤中的作用。
将大鼠分为5组。对照组（CG，n = 8）未接受任何处理，生理盐水组（SISG，n = 11）给予无菌等渗盐溶液，ICAM-1抗体组（ICAMG，n = 12）给予针对大鼠ICAM-1的单克隆抗体，别嘌醇组（ALLOG，n = 12）给予别嘌醇，亚甲蓝组（MBG，n = 14）给予亚甲蓝。进行60分钟的肠道缺血，随后再灌注60分钟。在再灌注前10分钟将药物注射给动物。再灌注60分钟后，采集血浆样本检测髓过氧化物酶（MPO）活性、肿瘤坏死因子α（TNF-α）和尿酸水平，并取回肠和空肠的肠道活检组织进行组织病理学检查。
与生理盐水组相比，别嘌醇组和ICAM-1抗体组的黏膜损伤减轻，TNF-α水平显著降低。ICAM-1抗体组的MPO活性最低，与其他组相比，别嘌醇组的尿酸水平显著降低。亚甲蓝降低了对再灌注损伤的TNF-α反应，但显著增加了黏膜损伤程度和MPO活性。
本研究表明，在再灌注前应用别嘌醇和针对黏附分子ICAM-1的单克隆抗体可能减轻肠道缺血再灌注造成的损伤，但在得出最终结论之前，还应在同一实验模型中研究不同的给药时间点、在不同缺血和再灌注持续时间下观察到的效果以及长期结果。亚甲蓝对预防或减轻肠道组织损伤无效，但由于这是第一项研究亚甲蓝对肠道再灌注损伤作用的研究，因此需要进一步研究不同剂量、缺血持续时间和给药时间的情况。
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