Department of Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium.
Abdominal Transplantation Laboratory, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium.
Int J Mol Sci. 2023 Jun 28;24(13):10775. doi: 10.3390/ijms241310775.
Intestinal ischemia-reperfusion injury (IRI) is a common clinical entity, and its outcome is unpredictable due to the triad of inflammation, increased permeability and bacterial translocation. Polyethylene glycol (PEG) is a polyether compound that is extensively used in pharmacology as an excipient in various products. More recently, this class of products have shown to have potent anti-inflammatory, anti-apoptotic, immunosuppressive and cell-membrane-stabilizing properties. However, its effects on the outcome after intestinal IRI have not yet been investigated. We hypothesized that PEG administration would reduce the effects of intestinal IRI in rodents. In a previously described rat model of severe IRI (45 min of ischemia followed by 60 min of reperfusion), we evaluated the effect of IV PEG administration at different doses (50 and 100 mg/kg) before and after the onset of ischemia. In comparison to control animals, PEG administration stabilized the endothelial glycocalyx, leading to reduced reperfusion edema, bacterial translocation and inflammatory reaction as well as improved 7-day survival. These effects were seen both in a pretreatment and in a treatment setting. The fact that this product is readily available and safe should encourage further clinical investigations in settings of intestinal IRI, organ preservation and transplantation.
肠缺血再灌注损伤(IRI)是一种常见的临床病症,由于炎症、通透性增加和细菌易位的三联征,其预后难以预测。聚乙二醇(PEG)是一种聚醚化合物,在药理学中被广泛用作各种产品的赋形剂。最近,这类产品显示出具有强大的抗炎、抗凋亡、免疫抑制和细胞膜稳定作用。然而,其对肠 IRI 后结局的影响尚未得到研究。我们假设 PEG 给药会减少啮齿动物肠 IRI 的影响。在先前描述的严重 IRI 大鼠模型(缺血 45 分钟,再灌注 60 分钟)中,我们评估了在缺血开始前后给予不同剂量(50 和 100mg/kg)的 IV PEG 给药的效果。与对照组动物相比,PEG 给药稳定了内皮糖萼,导致再灌注水肿、细菌易位和炎症反应减少,并提高了 7 天存活率。这些作用在预处理和治疗设置中都有观察到。鉴于该产品易于获得且安全,应鼓励在肠 IRI、器官保存和移植的情况下进行进一步的临床研究。