Milstein Dan M J, Bezemer Rick, Lindeboom Jérôme A H, Ince Can
Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Cancer Chemother Pharmacol. 2009 Oct;64(5):1047-52. doi: 10.1007/s00280-009-1082-x. Epub 2009 Jul 25.
A high incidence of oral complications is associated with chemotherapy (CT) treatment in cancer patients; however, while knowledge into molecular mechanisms of their pathobiology continue to evolve, the direct physiological effects of CT on oral tissue perfusion remain unexplored. The aim of this investigation was to assess the acute effects of CT on gingival microcirculation perfusion by measuring gingival capillary density.
Twenty female specific-pathogen free New Zealand White rabbits were randomly divided into four groups receiving four different intravenous dose levels of cyclophosphamide, methotrexate, and fluorouracil (CMF). Noninvasive measurements of gingival capillary density were performed using sidestream dark-field (SDF) imaging prior to and 30 min after CT treatment. Four rabbits receiving saline solution were used as control animals.
Baseline gingival capillary density was 58 +/- 11 cpll/mm(2), no significant differences in baseline capillary densities between the groups were found. From low to high dose CT, capillary density 30 min after CMF treatment increased in each group by 1 +/- 7, 5 +/- 7, 13 +/- 18 and 20 +/- 13 cpll/mm(2), respectively. Capillary density increase was significant in the high-dose group. No change in gingival capillary density was found in the control group.
Periodontal microcirculation perfusion had increased 30 min after CT treatment as indicated by a rise in gingival capillary density. Our results support the idea that CT-induced microcirculatory response not only diligently delivers but also saturates peripheral oral tissues with antineoplastic agents by increasing surface area exposure. This functional response of the microcirculation to CT drugs may play a role in contribution to oral complications and the treatment of oral tumors.
癌症患者化疗（CT）治疗常伴有较高的口腔并发症发生率；然而，尽管对其病理生物学分子机制的认识不断发展，但CT对口腔组织灌注的直接生理影响仍未得到探索。本研究的目的是通过测量牙龈毛细血管密度来评估CT对牙龈微循环灌注的急性影响。
将20只无特定病原体的雌性新西兰白兔随机分为四组，分别接受四种不同静脉剂量水平的环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF）。在CT治疗前和治疗后30分钟，使用侧流暗场（SDF）成像对牙龈毛细血管密度进行无创测量。四只接受生理盐水的兔子作为对照动物。
基线牙龈毛细血管密度为58±11个毛细血管/mm²，各组之间的基线毛细血管密度无显著差异。从低剂量到高剂量CT，CMF治疗后30分钟，每组的毛细血管密度分别增加了1±7、5±7、13±18和20±13个毛细血管/mm²。高剂量组的毛细血管密度增加显著。对照组的牙龈毛细血管密度无变化。
CT治疗后30分钟，牙龈毛细血管密度升高，表明牙周微循环灌注增加。我们的结果支持这样一种观点，即CT诱导的微循环反应不仅能勤奋地输送抗肿瘤药物，还能通过增加表面积暴露使外周口腔组织饱和。微循环对CT药物的这种功能反应可能在口腔并发症的发生和口腔肿瘤的治疗中起作用。
