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在宫颈炎实验大鼠模型中,硫糖铝调节尿激酶型纤溶酶原激活物受体(uPAR)和表皮生长因子受体(EGFR)的表达。

Sucralfate modulates uPAR and EGFR expression in an experimental rat model of cervicitis.

作者信息

Mannari C, Santi S, Migliori M, Filippi C, Origlia N, Sansò M, Boldrini E, Giovannini L

机构信息

Department of Neuroscience, Pharmacology section, University of Pisa, Pisa, Italy.

出版信息

Int J Immunopathol Pharmacol. 2008 Jul-Sep;21(3):651-8. doi: 10.1177/039463200802100319.

Abstract

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western blot and Immunohistochemistry techniques. Western blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.

摘要

硫糖铝是一种用于治疗胃和十二指肠溃疡的药物;它具有细胞保护作用,能够提高多种生长因子的生物利用度,调节伤口愈合过程。在本研究中,我们测试了硫糖铝治疗子宫颈溃疡性病变的可能疗效;为了研究这种疗效,我们使用了一种宫颈炎实验大鼠模型,评估了其中尿激酶型纤溶酶原激活物受体(uPAR)和表皮生长因子受体(EGFR)的表达。通过用浸有醋酸的棉球在野生型和去卵巢的Wistar雌性大鼠中诱发宫颈炎。将动物分为两个主要组(4天组和7天组),局部给予硫糖铝直至处死它们的那天。为了区分生理性愈合和药物诱导的愈合,使用蛋白质印迹法和免疫组织化学技术评估uPAR和EGFR表达的定量和定性情况。蛋白质印迹分析表明,在野生型和去卵巢动物受伤4天后,两种受体的表达均增加。特别是在去卵巢动物中,uPAR和EGFR的表达在4天后增加,而在给予硫糖铝后降低。在野生大鼠中,uPAR表达观察到相同情况,而EGFR则不同;事实上,在用药物治疗的动物中,其表达在第4天显著增加,而在未治疗的动物中仅在第7天增加。免疫组织化学显示,在用硫糖铝治疗的动物中,4天后EGFR和uPAR在上皮中有显著的共定位。我们得出结论,硫糖铝可以促进溃疡性宫颈炎的愈合,此外,由于其对uPAR和EGFR表达的调节特性,它还缩短了正常愈合时间。

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