Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Arch Oral Biol. 2011 Jun;56(6):599-606. doi: 10.1016/j.archoralbio.2010.11.015. Epub 2010 Dec 15.
The use of intravenous nitrogenous bisphosphonates and antineoplastic agents as postoperative adjuvant cancer management strategies may influence the course of oral wound healing by altering tissue vascularisation kinetics. The aim of this study was to investigate if single or combined zoledronic acid (ZOL) and cyclophosphamide (CTX) would influence microcirculation regeneration in healing oral mucosal flaps. Twenty female specific-pathogen free New Zealand white rabbits were randomised into four groups. In all animals a mucosal flap was raised; three groups were treated each separately with intravenous infusions of 0.14mg/kg ZOL, 100mg/kg CTX, or both, respectively. The fourth group was used as a control. Capillary density measurements, expressed as the mean number of capillaries±SD per mm(2) (cpll/mm(2)), was performed preoperatively using sidestream dark-field (SDF) imaging and repeated immediately postoperatively and on days 2, 4, 7, 9, 11, 14, and 21. Whole blood count and body weight was assessed in each group to monitor pharmacotherapeutic responses. Preoperative mean capillary density was 74±8cpll/mm(2) and 40±11cpll/mm(2) directly after surgery (P<0.0001). Post hoc comparisons of follow-up SDF measurements on days 9-21 between control and ZOL vs. CTX and ZOL+CTX were statistically significant (P<0.05). The present study demonstrates that ZOL did not alter capillary regeneration in healing mucosal flaps. However, although the early healing phase is generally characterised by rapid progression of capillary regeneration, interventions with CTX and ZOL+CTX significantly altered capillary regeneration and persisted beyond the third postoperative week.
静脉内氮双膦酸盐和抗肿瘤药物作为术后辅助癌症治疗策略的使用可能通过改变组织血管生成动力学来影响口腔伤口愈合的过程。本研究的目的是研究单独或联合使用唑来膦酸（ZOL）和环磷酰胺（CTX）是否会影响愈合口腔黏膜瓣的微循环再生。将 20 只无特定病原体的雌性新西兰白兔随机分为四组。所有动物均行黏膜瓣掀起术；三组分别单独给予静脉输注 0.14mg/kg ZOL、100mg/kg CTX 或两者联合。第四组作为对照。使用边流暗场（SDF）成像术术前进行毛细血管密度测量，以每平方毫米的毛细血管数（cpll/mm²）表示，并在术后即刻以及第 2、4、7、9、11、14 和 21 天重复测量。每组均进行全血细胞计数和体重评估，以监测药物治疗反应。术前平均毛细血管密度为 74±8cpll/mm²，术后即刻为 40±11cpll/mm²（P<0.0001）。术后第 9-21 天 SDF 随访测量的组间比较，对照组与 ZOL 组、CTX 组与 ZOL+CTX 组之间有统计学意义（P<0.05）。本研究表明 ZOL 不会改变愈合黏膜瓣中的毛细血管再生。然而，尽管早期愈合阶段通常以毛细血管再生的快速进展为特征，但 CTX 和 ZOL+CTX 的干预显著改变了毛细血管再生，并持续至术后第三周。
