Polyethylene Glycol Preconditioning: An Effective Strategy to Prevent Liver Ischemia Reperfusion Injury.
Polyethylene Glycol Preconditioning: An Effective Strategy to Prevent Liver Ischemia Reperfusion Injury.
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DOI：
10.1155/2016/9096549
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发表时间：
2016
影响因子：
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通讯作者：
Roselló-Catafau J
中科院分区：
文献类型：
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作者：
Bejaoui M;Pantazi E;Calvo M;Folch-Puy E;Serafín A;Pasut G;Panisello A;Adam R;Roselló-Catafau J
肝脏缺血再灌注损伤(IRI)是肝脏外科手术中不可避免的临床问题。聚乙二醇(PEGS)是一种水溶性、无毒的聚合物，已在各种体内和体外组织损伤模型中证明了其有效性。本研究旨在探讨静脉注射35 kDa的高分子量聚乙二醇35(PEG35)是否可作为大鼠肝脏缺血再灌注损伤的一种有效的预适应策略。给雄性SD大鼠静脉注射PEG35，剂量分别为2和10 mg/kg。然后，大鼠进行1小时的部分缺血(70%)，然后再灌流2小时。结果表明，静脉注射10 mg/kg的PEG35对大鼠肝脏缺血再灌注损伤有明显的保护作用。转氨酶水平的显著降低和线粒体膜极化的更好保存证明了这一点。此外，PEG35保留了肝细胞的形态，反映在F-肌动蛋白/G-肌动蛋白比率的增加和共聚焦显微镜下的发现。此外，PEG35的保护机制与激活细胞存活蛋白Akt和细胞保护因子AMPK以及抑制细胞凋亡有关。因此，聚乙二醇可望成为一种合适的药物预适应药物来对抗肝脏IRI。
Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proven their effectiveness in various in vivo and in vitro models of tissue injury. The present study aims to investigate whether the intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) could be an effective strategy for rat liver preconditioning against IRI. PEG 35 was intravenously administered at 2 and 10 mg/kg to male Sprague Dawley rats. Then, rats were subjected to one hour of partial ischemia (70%) followed by two hours of reperfusion. The results demonstrated that PEG 35 injected intravenously at 10 mg/kg protected efficiently rat liver against the deleterious effects of IRI. This was evidenced by the significant decrease in transaminases levels and the better preservation of mitochondrial membrane polarization. Also, PEG 35 preserved hepatocyte morphology as reflected by an increased F-actin/G-actin ratio and confocal microscopy findings. In addition, PEG 35 protective mechanisms were correlated with the activation of the prosurvival kinase Akt and the cytoprotective factor AMPK and the inhibition of apoptosis. Thus, PEG may become a suitable agent to attempt pharmacological preconditioning against hepatic IRI.