Department of General, Visceral and Transplant Surgery, University of Tübingen, Germany.
J Surg Res. 2011 May 1;167(1):158-65. doi: 10.1016/j.jss.2009.07.013. Epub 2009 Aug 11.
Delayed wound healing is a serious side effect of mTOR inhibitor-based immunosuppression after solid organ transplantation. The aim of this study was to test the hypothesis that the mTOR inhibitor everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses.
Thirty male Sprague-Dawley rats received a colonic anastomosis. Then, animals were randomized to three groups of daily treatment with either vehicle or everolimus in two different dosages (1.0mg/kg or 3.0mg/kg). After 7 d, rats were sacrificed, and mechanical, histologic, and biochemical parameters of intestinal healing were assessed.
Anastomotic bursting pressure was significantly decreased by everolimus in both dosages, whereas hydroxyproline content was reduced only by the high everolimus dosage. Everolimus diminished cellular proliferation and new vessel growth. Furthermore, both quantity as well as quality of newly synthesized collagen fibers in the anastomotic granulation tissue was reduced. On the other hand, myeloperoxidase-positive (MPO) cells and interleukin-6 (IL-6) concentrations were increased, as was the activity of matrix-metalloproteinases MMP-2 and MMP-9.
Everolimus interferes with the inflammatory phase of healing. However, it remains unclear whether this phenomenon is involved in everolimus impairment of experimental anastomotic repair.
mTOR 抑制剂为基础的免疫抑制是实体器官移植后延迟伤口愈合的严重副作用。本研究旨在验证 mTOR 抑制剂依维莫司是否会干扰实验性结肠吻合术愈合的炎症期的假说。
30 只雄性 Sprague-Dawley 大鼠接受结肠吻合术。然后，动物随机分为三组，每天接受载体或依维莫司两种不同剂量（1.0mg/kg 或 3.0mg/kg）的治疗。7d 后，处死大鼠，评估肠愈合的机械、组织学和生化参数。
两种剂量的依维莫司均显著降低吻合口爆裂压，而羟脯氨酸含量仅在高剂量依维莫司组降低。依维莫司减少了细胞增殖和新血管生长。此外，吻合口肉芽组织中新合成的胶原纤维的数量和质量均降低。另一方面，髓过氧化物酶阳性（MPO）细胞和白细胞介素 6（IL-6）浓度增加，基质金属蛋白酶 MMP-2 和 MMP-9 的活性也增加。
依维莫司干扰愈合的炎症期。然而，尚不清楚这种现象是否与依维莫司损害实验性吻合口修复有关。
