Rocha-Santos Vinicius, Figueira Estela R R, Rocha-Filho Joel A, Coelho Ana M M, Pinheiro Rafael Soraes, Bacchella Telesforo, Machado Marcel C C, D'Albuquerque Luiz A C
Department of Gastroenterology, Laboratory of Medical Investigations LIM37 Discipline of Liver and Gastrointestinal Transplantation and Discipline of Anesthesiology, Hospital das Clinicas, University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil.
Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):194-200. doi: 10.1016/s1499-3872(15)60348-4.
Liver ischemia reperfusion (IR) injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and hypertonic saline solution (HTS) have been identified to have beneficial effects against IR injury. This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury.
Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaCl plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase.
HPTX significantly decreased TNF-alpha 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion.
This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.
肝脏缺血再灌注(IR)损伤会引发全身炎症反应,是肝脏手术后器官功能障碍和不良术后结局的主要原因。已证实己酮可可碱(PTX)和高渗盐溶液(HTS)对IR损伤具有有益作用。本研究旨在探讨在HTS中添加PTX是否比单独使用HTS更能有效预防肝脏IR损伤。
将雄性Wistar大鼠分为三组。对照组大鼠经历60分钟的部分肝脏缺血,HTS组大鼠在再灌注前15分钟静脉注射0.4 mL/kg的7.5%氯化钠,HPTX组大鼠在再灌注前15分钟静脉注射7.5%氯化钠加25 mg/kg的PTX。再灌注后采集样本,测定谷丙转氨酶(ALT)、谷草转氨酶(AST)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、线粒体呼吸、脂质过氧化、肺通透性和髓过氧化物酶。
再灌注30分钟后,HPTX组的TNF-α显著降低。再灌注4小时后,HPTX组和HTS组的ALT、AST、IL-6、线粒体功能障碍和肺髓过氧化物酶显著降低。与单独使用HTS相比,HPTX组在再灌注4小时后显著降低了肝脏氧化应激,在再灌注4小时和12小时后显著降低了肺通透性。
本研究表明,PTX通过降低肝脏氧化应激和肺通透性增强了HTS对肝脏IR损伤的有益作用。