Tarhan Omer Ridvan, Barut Ibrahim, Sutcu Recep, Akdeniz Yusuf, Akturk Onur
Department of General Surgery, Suleyman Demirel University Medical School, Isparta, Turkey.
Tohoku J Exp Med. 2006 Jul;209(3):249-55. doi: 10.1620/tjem.209.249.
Peritoneum has an intrinsic fibrinolytic activity that breaks the peritoneal adhesions. Peritoneal injuries with ischemia interfere this fibrinolytic activity and cause adhesions. Pentoxifylline, a methyl xanthine derivative, improves blood flow by decreasing its viscosity and also increases fibrinolytic activity in plasma. We hypothesized that pentoxifylline would increase peritoneal fibrinolysis and ameliorate adhesions. A rat model of peritoneal adhesion (cecal abrasion with gauze, n = 15 for each group) was used to test this hypothesis and cardinal parameters of peritoneal fibrinolysis were measured in peritoneal samples. No medication was given in control animals, while pentoxifylline was administered intraperitonealy (IP) (25 mg/kg, before abdominal closure to whole abdomen) or intravenously (IV) (25 mg/kg, for 9 days after operation) in the experimental groups. At postoperative day 10, peritoneal biopsies were obtained and adhesions were graded qualitatively. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA/PAI-1 complex and hydroxyproline contents were determined. Total adhesion scores were decreased in both treated groups. Mean levels of tPA concentration and tPA activity were increased in the treated groups compared to controls (p < 0.001 and p = 0.001, respectively). The tPA/PAI-1 complex levels were similar among the three groups. PAI-1 levels were lower in animals receiving IP pentoxifylline compared to control animals and those treated with IV pentoxifylline (p = 0.048, p = 0.015, respectively). Peritoneal hydroxyproline levels were similar among the three groups. Our results suggest that pentoxifylline administration either through IV or IP may reduce peritoneal adhesion formation probably by altering peritoneal fibrinolytic activity.
腹膜具有内在的纤维蛋白溶解活性，可分解腹膜粘连。伴有局部缺血的腹膜损伤会干扰这种纤维蛋白溶解活性并导致粘连。己酮可可碱是一种甲基黄嘌呤衍生物，可通过降低血液粘度来改善血流，还能增加血浆中的纤维蛋白溶解活性。我们推测己酮可可碱会增强腹膜纤维蛋白溶解并改善粘连情况。采用腹膜粘连大鼠模型（用纱布擦伤盲肠，每组n = 15）来验证这一假设，并在腹膜样本中测量腹膜纤维蛋白溶解的主要参数。对照组动物不给予任何药物，而在实验组中，己酮可可碱通过腹腔内注射（IP）（25 mg/kg，在腹部缝合前注入全腹）或静脉注射（IV）（25 mg/kg，术后9天）给药。术后第10天，获取腹膜活检组织并对粘连进行定性分级。测定组织型纤溶酶原激活剂（tPA）、1型纤溶酶原激活剂抑制剂（PAI-1）、tPA/PAI-1复合物的活性和浓度以及羟脯氨酸含量。两个治疗组的总粘连评分均降低。与对照组相比，治疗组中tPA浓度和tPA活性的平均水平升高（分别为p < 0.001和p = 0.001）。三组之间tPA/PAI-1复合物水平相似。与对照组动物和接受静脉注射己酮可可碱治疗的动物相比，接受腹腔内注射己酮可可碱的动物的PAI-1水平较低（分别为p = 0.048，p = 0.015）。三组之间腹膜羟脯氨酸水平相似。我们的结果表明，通过静脉注射或腹腔内注射给予己酮可可碱可能通过改变腹膜纤维蛋白溶解活性来减少腹膜粘连的形成。
