神经激肽 1 受体拮抗剂可减少术后腹膜粘连形成并增加腹膜纤溶活性。,Proceedings of the National Academy of Sciences of the United States of America

当前位置： X-MOL 学术 › Proc. Natl. Acad. Sci. U.S.A. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

神经激肽 1 受体拮抗剂可减少术后腹膜粘连形成并增加腹膜纤溶活性。
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2004 Jun 15 , DOI: 10.1073/pnas.0403210101
Karen L Reed ₁ , A Brent Fruin , Adam C Gower , Arthur F Stucchi , Susan E Leeman , James M Becker

Affiliation

纤维粘连仍然是腹部手术的主要后遗症。促炎肽物质 P (SP) 已知参与炎症事件，可能在粘附形成中发挥关键作用。该假设通过使用拮抗剂 CJ-12,255（辉瑞）进行了测试，该拮抗剂可阻断 SP 与神经激肽 1 受体 (NK-1R) 的结合。通过手术在接受每日剂量的 NK-1R 拮抗剂（NK-1RA；每天 5.0 或 10.0 mg/kg）或盐水的大鼠腹膜中诱导粘连形成。术后第 7 天，与对照组相比，低剂量和高剂量 NK-1RA 均显着（P < 0.05）分别减少粘连形成 45% 和 53%。随后，研究了 NK-1RA 给药对腹膜纤溶活性的影响，以确定 SP 在腹膜中作用的潜在机制。从未手术对照和术后 24 小时施用 NK-1RA 或盐水的动物收集样本。通过酶谱法测定腹膜液中的纤溶活性，并分别通过 RT-PCR 和生物测定法评估腹膜组织和腹膜液中纤溶活性调节剂组织纤溶酶原激活剂 (tPA) 和纤溶酶原激活剂抑制剂 1 的表达。与未手术和施用盐水的动物相比，NK-1RA 施用导致腹膜组织中 tPA mRNA 水平显着增加（P < 0.05）。同样，NK-1RA 给药显着（P < 0.05）增加腹膜液中的 tPA。这些数据表明，NK-1R 的激活通过限制术后腹膜的纤溶活性来促进腹膜粘连的形成，从而使纤维蛋白粘连持续存在。

"点击查看英文标题和摘要"

A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity.

Fibrous adhesions remain a major sequela of abdominal surgery. The proinflammatory peptide substance P (SP), known to participate in inflammatory events, may play a key role in adhesion formation. This hypothesis was tested by using an antagonist, CJ-12,255 (Pfizer), that blocks the binding of SP to the neurokinin 1 receptor (NK-1R). Adhesion formation was surgically induced in the peritoneum of rats receiving daily doses of the NK-1R antagonist (NK-1RA; 5.0 or 10.0 mg/kg per day) or saline. On postoperative day 7, both the low and high doses of NK-1RA significantly (P < 0.05) reduced adhesion formation by 45% and 53%, respectively, compared with controls. Subsequently, the effect of NK-1RA administration on peritoneal fibrinolytic activity was investigated to determine a potential mechanism for SP action in the peritoneum. Samples were collected from nonoperated controls and from animals 24 h postsurgery that were administered either NK-1RA or saline. Fibrinolytic activity in peritoneal fluid was assayed by zymography, and expression of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1, both regulators of fibrinolytic activity, was assessed in peritoneal tissue and fluid by RT-PCR and bioassay, respectively. NK-1RA administration led to a marked (P < 0.05) increase in tPA mRNA levels in peritoneal tissue compared with nonoperated and saline-administered animals. Likewise, NK-1RA administration significantly (P < 0.05) increased tPA in the peritoneal fluid. These data suggest that activation of the NK-1R promotes peritoneal adhesion formation by limiting fibrinolytic activity in the postoperative peritoneum, thus enabling fibrinous adhesions to persist.

更新日期：2017-01-31

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南