Pino Danilo Siqueira, Casarin Renato Correa, Pimentel Suzana Peres, Cirano Fabiano Ribeiro, Corrêa Mônica Grazieli, Ribeiro Fernanda Vieira
Student, Dental Research Division, School of Dentistry, Paulista University, São Paulo, SP, Brazil.
Professor, Dental Research Division, School of Dentistry, Paulista University, São Paulo, SP, Brazil.
J Oral Maxillofac Surg. 2017 Dec;75(12):2561.e1-2561.e10. doi: 10.1016/j.joms.2017.07.167. Epub 2017 Aug 3.
This study investigated the influence of resveratrol (RESV) on the repair of bone critical defects in calvaria of animals with induced diabetes mellitus (DM).
One hundred rats were divided into 5 groups: induced DM + RESV administration (DM + RESV; n = 20); induced DM plus placebo solution administration (DM + PLAC; n = 20); induced DM plus insulin therapy (DM + INS; n = 20); induced DM plus administration of RES and INS (DM + RESV + INS; n = 20); and nondiabetic controls (NDM; n = 20). DM was induced by intraperitoneal injection of streptozotocin 50 mg/kg 3 days before the surgical procedures. Two critical calvarial defects were created in each animal at the start of the study (day 0). Treatments were administered from day 0 to day 30 of the experiment, when animals were euthanized. One defect was processed for histometric analysis to measure closure of the bone defect. The tissue of the other defect was analyzed for quantification of bone morphogenetic protein-2 (BMP-2), osteopontin, osteoprotegerin, receptor activator of nuclear factor-κB ligand, runt-related transcription factor-2, osterix (Osx), β-catenin, lipoprotein receptor-related protein-5, and dikkop-1 mRNA by quantitative polymerase chain reaction.
Histometric results showed that the DM + RESV, DM + RESV + INS, and NDM groups exhibited greater closure of the bone defects compared with the PLAC- or INS-treated groups (P < .05). Diabetic animals treated with RESV plus INS showed higher levels of BMP-2 and Osx; Osx also was positively increased in animals treated with INS alone (P < .05).
The use of RESV, regardless of the presence of INS, positively influenced bone repair in animals with induced DM. Further, the combination of INS plus RESV was necessary for the modulation of BMP-2 gene expression.
本研究调查了白藜芦醇（RESV）对诱导性糖尿病（DM）动物颅骨关键骨缺损修复的影响。
100只大鼠分为5组：诱导性DM + RESV给药组（DM + RESV；n = 20）；诱导性DM加安慰剂溶液给药组（DM + PLAC；n = 20）；诱导性DM加胰岛素治疗组（DM + INS；n = 20）；诱导性DM加RES和INS给药组（DM + RESV + INS；n = 20）；以及非糖尿病对照组（NDM；n = 20）。在手术前3天通过腹腔注射链脲佐菌素50 mg/kg诱导DM。在研究开始时（第0天），每只动物制造两个关键颅骨缺损。从实验第0天至第30天给予治疗，之后对动物实施安乐死。一个缺损用于组织计量学分析以测量骨缺损的闭合情况。另一个缺损的组织通过定量聚合酶链反应分析骨形态发生蛋白-2（BMP-2）、骨桥蛋白、骨保护素、核因子κB受体激活剂配体、 runt相关转录因子-2、osterix（Osx）、β-连环蛋白、脂蛋白受体相关蛋白-5和dikkop-1 mRNA的定量。
组织计量学结果显示，与PLAC或INS治疗组相比，DM + RESV、DM + RESV + INS和NDM组的骨缺损闭合程度更大（P < 0.05）。用RESV加INS治疗的糖尿病动物显示出更高水平的BMP-2和Osx；单独用INS治疗的动物中Osx也呈阳性增加（P < 0.05）。
无论是否存在INS，RESV的使用对诱导性DM动物的骨修复有积极影响。此外，INS加RESV的组合对于调节BMP-2基因表达是必要的。
