Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710061, People's Republic of China.
Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
Sci Rep. 2017 Aug 30;7(1):10001. doi: 10.1038/s41598-017-10582-w.
The aim of the present study is to investigate the role and potential mechanisms of peripheral serotonin in postoperative intra-abdominal adhesion formation in mice. The caecum-rubbing operations were conducted for intra-abdominal adhesion formation modelling in wild-type and Tph1-/- mice. The deficiency of serotonin significantly decreased the adhesion scores, weight loss, and adhesion thickness as well as levels of collagen fibres and hydroxyproline in the adhesive tissues. The Tph1-/- mice exhibited a milder inflammatory response and oxidative stress in the adhesive tissues than did the wild-type mice. Moreover, the deficiency of serotonin reduced the levels of PAI-1 and fibrinogen, and raised the t-PA and t-PA/PAI levels in the peritoneal fluids. Moreover, the expressions of CD34, VEGF, TGF-β and 5-HT receptor in the adhesive tissues were significantly decreased in the Tph1-/- group mice. Furthermore, the Tph1-/- +5-HTP group showed more severe adhesions than did the Tph1-/- group mice, and the p-chlorophenylalanine (PCPA) could markedly alleviated the adhesion formation in the WT mice. In conclusion, the present study showed that peripheral serotonin regulated postoperative intra-abdominal adhesion formation by facilitating inflammation, oxidative stress, disorder of the fibrinolytic system, angiopoiesis and TGF-β1 expression via the 5-HT receptor in the adhesive tissues.
本研究旨在探讨外周 5-羟色胺在小鼠术后腹腔粘连形成中的作用及其潜在机制。采用盲肠摩擦法构建腹腔粘连模型,分别在野生型和 Tph1-/- 小鼠中进行。5-羟色胺缺乏显著降低了粘连评分、体重减轻、粘连厚度以及粘连组织中胶原纤维和羟脯氨酸的水平。与野生型小鼠相比,Tph1-/- 小鼠的粘连组织炎症反应和氧化应激较轻。此外,5-羟色胺缺乏降低了腹腔液中 PAI-1 和纤维蛋白原的水平,提高了 t-PA 和 t-PA/PAI 的水平。此外,粘连组织中 CD34、VEGF、TGF-β 和 5-HT 受体的表达在 Tph1-/- 组小鼠中明显降低。此外,Tph1-/-+5-HTP 组小鼠的粘连程度比 Tph1-/- 组更严重,而对氯苯丙氨酸(PCPA)可显著减轻 WT 小鼠的粘连形成。综上所述,本研究表明,外周 5-羟色胺通过促进炎症、氧化应激、纤溶系统紊乱、血管生成和 TGF-β1 表达,调节粘连组织中的 5-HT 受体,从而影响术后腹腔粘连的形成。