de Campos Tercio, Deree Jessica, Martins Joilson O, Loomis William H, Shenvi Edna, Putnam James G, Coimbra Raul
Division of Trauma and Surgical Critical Care, Department of Surgery, University of California School of Medicine, San Diego, CA, USA.
Pancreas. 2008 Jul;37(1):42-9. doi: 10.1097/MPA.0b013e3181612d19.
Acute pancreatitis (AP) is associated with a systemic inflammatory response. Pentoxifylline (PTX) has been shown to attenuate neutrophil activation and end-organ injury in shock states such as hemorrhage and sepsis. We hypothesized that PTX would down-regulate AP-induced lung injury.
Sprague-Dawley rats underwent catheterization of the pancreatic duct. Acute pancreatitis (n = 7) and AP/PTX animals (n = 7) received a retrograde infusion of 3.5% sodium taurocholate and intravenous treatment with normal saline or normal saline and PTX (25 mg/kg), respectively. Pulmonary neutrophil degranulation and sequestration were determined by zymography and detection of myeloperoxidase. Nuclear factor kappa B and mitogen-activated protein kinase phosphorylation was determined by Western blot. Cytokine-induced neutrophil chemoattractant was quantified by enzyme linked immunosorbent assay.
Pulmonary histologic injury scores were attenuated in the AP/PTX group (P < 0.05). Plasma amylase levels remained unchanged. Pentoxifylline produced a significant decline in myeloperoxidase content and matrix metalloproteinase activity (P < 0.05). The increase in the phosphorylation of pulmonary nuclear factor kappa B, p38 mitogen-activated protein kinase, and extracellular-related signal kinase 1/2 observed after AP was not demonstrated with PTX (P < 0.05). Pentoxifylline supplementation reduced pulmonary cytokine-induced neutrophil chemoattractant levels by 50% (P < 0.05).
Pentoxifylline significantly attenuated histologic lung injury, pulmonary neutrophil activity, and proinflammatory signaling in a severe model of AP. Therefore, PTX may serve as an adjunct for the treatment of the inflammatory complications of severe AP.
急性胰腺炎（AP）与全身炎症反应相关。已表明己酮可可碱（PTX）可减轻诸如出血和脓毒症等休克状态下的中性粒细胞活化及终末器官损伤。我们推测PTX会下调AP诱导的肺损伤。
将Sprague-Dawley大鼠进行胰管插管。急性胰腺炎组（n = 7）和AP/PTX组动物（n = 7）分别接受逆行输注3.5%牛磺胆酸钠，并分别静脉注射生理盐水或生理盐水加PTX（25 mg/kg）。通过酶谱法和髓过氧化物酶检测来测定肺中性粒细胞脱颗粒和滞留情况。通过蛋白质免疫印迹法测定核因子κB和丝裂原活化蛋白激酶磷酸化。通过酶联免疫吸附测定法定量细胞因子诱导的中性粒细胞趋化因子。
AP/PTX组的肺组织学损伤评分降低（P < 0.05）。血浆淀粉酶水平保持不变。己酮可可碱使髓过氧化物酶含量和基质金属蛋白酶活性显著下降（P < 0.05）。PTX未显示出AP后观察到的肺核因子κB、p38丝裂原活化蛋白激酶和细胞外相关信号激酶1/2磷酸化的增加（P < 0.05）。补充己酮可可碱使肺细胞因子诱导的中性粒细胞趋化因子水平降低了50%（P < 0.05）。
在严重的AP模型中，己酮可可碱显著减轻了组织学肺损伤、肺中性粒细胞活性和促炎信号传导。因此，PTX可作为治疗严重AP炎症并发症的辅助药物。
