Division of Digestive Tract Transplantation (LIM/37), Department of Gastroenterology, University of São Paulo, São Paulo, Brazil.
HPB (Oxford). 2013 Aug;15(8):588-94. doi: 10.1111/hpb.12013. Epub 2012 Dec 17.
Therapeutic strategies to reduce the occurrence of pancreatic ischaemia-reperfusion (I-R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti-inflammatory effect by inhibiting NF-κB activation. This group has previously demonstrated that pentoxifylline induces an anti-inflammatory response in acute pancreatitis and liver I-R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I-R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I-R injury.
Pancreatic I-R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I-R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed.
Significant reductions in serum TNF-α, IL-6 and IL-10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline-treated animals, denoting less severe pancreatic histologic damage.
Pentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I-R injury and may be a useful tool in pancreas and kidney transplantation.
减少胰腺缺血再灌注（I-R）损伤发生的治疗策略可能会改善人类胰腺和肾脏移植的结果。己酮可可碱除了具有血液流变学作用外，还通过抑制 NF-κB 激活发挥抗炎作用。该小组先前证明，己酮可可碱可诱导急性胰腺炎和肝 I-R 模型中的抗炎反应。这导致了这样的假设，即己酮可可碱可能会减少胰腺和肾脏损伤以及胰腺 I-R 损伤中的全身炎症反应。本实验研究的目的是评估己酮可可碱在大鼠胰腺 I-R 损伤模型中的作用。
通过夹闭脾血管，在 Wistar 大鼠中进行 1 小时的胰腺 I-R。将经历 I-R 的动物分为两组：第 1 组（n = 20，对照组）大鼠在缺血后 45 分钟接受静脉注射生理盐水，第 2 组（n = 20）大鼠在缺血后 45 分钟接受静脉注射己酮可可碱（25 mg/kg）。采集血样以测定淀粉酶、肌酐、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）。还评估了胰腺丙二醛（MDA）含量、胰腺组织学和肺髓过氧化物酶（MPO）。
与第 1 组相比，第 2 组的血清 TNF-α、IL-6 和 IL-10 显著降低（P < 0.05）。两组之间的胰腺 MDA 含量或血清淀粉酶水平没有差异。己酮可可碱治疗的动物的组织学评分明显较低，表明胰腺组织学损伤较轻。
己酮可可碱的给药减少了胰腺 I-R 损伤中的全身炎症反应、胰腺组织学病变和肾功能障碍，可能是胰腺和肾脏移植的有用工具。
