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非侵入性检测化疗诱导的大鼠远端小肠损伤后,由培非格司亭介导的适应性反应。

Non-invasive detection of a palifermin-mediated adaptive response following chemotherapy-induced damage to the distal small intestine of rats.

机构信息

Gastroenterology Department, Children Youth and Women's Health Services, North Adelaide, Australia.

出版信息

Cancer Biol Ther. 2011 Sep 1;12(5):399-406. doi: 10.4161/cbt.12.5.15977.

Abstract

INTRODUCTION

Pre-clinical studies have indicated that palifermin may be an effective treatment modality for intestinal mucositis, a debilitating complication of cancer chemotherapy. We determined whether palifermin was protective in rats with experimentally induced intestinal mucositis and the applicability of the sucrose breath test (SBT) to monitor palifermin for its efficacy as an anti-mucositis agent.

RESULTS

SBT values and sucrase activity were reduced in all 5-FU-treated groups compared with untreated controls (p < 0.05). At 72 h post 5-FU, sucrase activity was higher in rats treated with palifermin compared with 5-FU controls (p < 0.05). Jejunal and ileal villus heights were lower in all 5-FU groups compared with saline controls.

METHODS

Dark agouti rats (n = 10) were subcutaneously injected with palifermin or vehicle for 3 d after which they were injected with 5-fluorouracil (5-FU) and sacrificed after 72 h. The in vivo SBT and in vitro sucrase assay were used to evaluate small intestinal function and damage. Intestinal disease severity was determined by histological assessment of villus height and crypt depth.

CONCLUSION

The SBT can monitor the ability of palifermin to modify the functional capacity of the small intestine in rats with intestinal mucositis. Further studies are indicated to investigate the prophylactic potential of palifermin against intestinal mucositis.

摘要

简介

临床前研究表明,培非格司亭可能是一种治疗肠道黏膜炎的有效方法,这是癌症化疗的一种衰弱性并发症。我们确定了培非格司亭是否对实验诱导的肠道黏膜炎大鼠具有保护作用,以及蔗糖呼气试验(SBT)是否适用于监测培非格司亭作为抗黏膜炎药物的疗效。

结果

与未处理的对照组相比,所有 5-FU 处理组的 SBT 值和蔗糖酶活性均降低(p < 0.05)。在 5-FU 后 72 小时,用培非格司亭治疗的大鼠的蔗糖酶活性高于 5-FU 对照组(p < 0.05)。与生理盐水对照组相比,所有 5-FU 组的空肠和回肠绒毛高度均较低。

方法

暗褐家鼠(n = 10)在皮下注射培非格司亭或载体 3 天后,用 5-氟尿嘧啶(5-FU)注射,并在 72 小时后处死。使用体内 SBT 和体外蔗糖酶测定法评估小肠功能和损伤。通过绒毛高度和隐窝深度的组织学评估确定肠道疾病严重程度。

结论

SBT 可以监测培非格司亭在患有肠道黏膜炎的大鼠中改变小肠功能能力的能力。需要进一步研究以探讨培非格司亭预防肠道黏膜炎的潜力。

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