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新型口服转化生长因子-β信号通路抑制剂能有效抑制术后粘连带形成。

Novel oral transforming growth factor-β signaling inhibitor potently inhibits postsurgical adhesion band formation.

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Cell Physiol. 2020 Feb;235(2):1349-1357. doi: 10.1002/jcp.29053. Epub 2019 Jul 17.

Abstract

Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-β type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients.

摘要

在这里,我们研究了转化生长因子-β 型 I 受体激酶抑制剂 EW-7197 对术后粘连带形成的治疗效果。我们的结果表明,这种药理抑制剂可预防小鼠模型中粘连带的形成频率和稳定性。我们还表明,下调促炎细胞因子、减少黏膜下水肿、减轻炎症细胞浸润、抑制氧化应激、减少过度胶原沉积以及抑制手术部位的促纤维化基因是 EW-7197 发挥其对粘连带形成的保护作用的部分机制。这些结果清楚地表明,EW-7197 具有治疗术后粘连带形成的新特性,具有抑制术后患者炎症和纤维化关键病理反应的临床转化潜力。

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