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局部应用缺氧诱导因子1-α增强剂去铁胺对预防药物相关性颌骨坏死是否有前景?

Could Local Application of Hypoxia Inducible Factor 1-α Enhancer Deferoxamine Be Promising for Preventing of Medication-Related Osteonecrosis of the Jaw?

作者信息

Yalcin-Ülker Gül Merve, Günbatan Murat, Duygu Gonca, Soluk-Tekkesin Merva, Özcakir-Tomruk Ceyda

机构信息

Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Istanbul Okan University, Istanbul 34947, Türkiye.

Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Tekirdag Namık Kemal University, Tekirdag 59030, Türkiye.

出版信息

Biomedicines. 2023 Mar 2;11(3):758. doi: 10.3390/biomedicines11030758.

Abstract

This experimental study investigates the prophylactic effect of deferoxamine (DFO) on medication-related osteonecrosis of the jaw (MRONJ). Thirty-six female Sprague Dawley rats received zoledronic acid (ZA) for eight weeks to create an osteonecrosis model. DFO was locally applied into the extraction sockets with gelatin sponge (GS) carriers to prevent MRONJ. The specimens were histopathologically and histomorphometrically evaluated. Hypoxia-inducible factor 1-alpha (HIF-1α) protein levels in the extraction sockets were quantified. New bone formation rate differed significantly between groups ( = 0.005). Newly formed bone ratios in the extraction sockets did not differ significantly between the control group and the GS ( = 1), GS/DFO ( = 0.749), ZA ( = 0.105), ZA-GS ( = 0.474), and ZA-GS/DFO ( = 1) groups. While newly formed bone rates were higher in the ZA-GS and ZA-GS/DFO groups than in the ZA group, the differences were not significant. HIF-1α levels differed significantly between groups ( < 0.001) and were significantly higher in the DFO and ZA-GS/DFO groups than in the control group ( = 0.001 and = 0.004, respectively). While HIF-1α levels were higher in the ZA-GS/DFO group than in the ZA group, the difference was not significant. While HIF-1α protein levels and new bone formation rate were elevated in the DFO-treated group, the effect was not significant. Further large-scale studies are needed to understand DFO's preventative effects on MRONJ and the role of HIF-1α in MRONJ pathogenesis.

摘要

本实验研究探讨去铁胺(DFO)对药物相关性颌骨坏死(MRONJ)的预防作用。36只雌性Sprague Dawley大鼠接受唑来膦酸(ZA)治疗8周以建立骨坏死模型。将DFO与明胶海绵(GS)载体局部应用于拔牙窝以预防MRONJ。对标本进行组织病理学和组织形态计量学评估。对拔牙窝中的缺氧诱导因子1α(HIF-1α)蛋白水平进行定量。各组之间的新骨形成率差异显著(=0.005)。对照组与GS组(=1)、GS/DFO组(=0.749)、ZA组(=0.105)、ZA-GS组(=0.474)和ZA-GS/DFO组(=1)的拔牙窝中新形成骨的比例差异不显著。虽然ZA-GS组和ZA-GS/DFO组的新骨形成率高于ZA组,但差异不显著。各组之间的HIF-1α水平差异显著(<0.001),DFO组和ZA-GS/DFO组的HIF-1α水平显著高于对照组(分别为=0.001和=0.004)。虽然ZA-GS/DFO组的HIF-1α水平高于ZA组,但差异不显著。虽然DFO治疗组的HIF-1α蛋白水平和新骨形成率有所升高,但效果不显著。需要进一步开展大规模研究以了解DFO对MRONJ的预防作用以及HIF-1α在MRONJ发病机制中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e499/10045901/eda8d417925a/biomedicines-11-00758-g001.jpg

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