Zheng Li Wu, Ma Li, Cheung Lim Kwong
Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, the University of Hong Kong.
Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, the University of Hong Kong.
Bone. 2008 Aug;43(2):355-361. doi: 10.1016/j.bone.2008.04.002. Epub 2008 Apr 16.
Nicotine is the main chemical in cigarettes responsible for the tobacco's pathological effects. The influence of nicotine on bone healing remains controversial. Distraction osteogenesis provides an ideal model to study bone healing and regeneration. The present study aims to evaluate the effects of nicotine on blood perfusion, angiogenesis and bone formation using a rabbit model of mandibular lengthening. Twenty adult New Zealand white rabbits were randomly assigned to the control group and nicotine group. The total nicotine or placebo exposure time for all animals was 7 weeks. After 2- or 4-week of consolidation following osteotomy, 3-day of latency and 11-day of active distraction, the animals were sacrificed and the mandibles were harvested. Blood perfusion and vascularization were evaluated by Laser Doppler monitoring and Collagen IV immunohistochemistry staining respectively. Bone formation was assessed by radiological, histological and immunohistochemical examination. Results showed that nicotine exposure increased microvessel density, whereas inhibited blood flow and bone formation. The expression of bone morphogenetic protein (BMP)-2 in osteoblasts was also decreased. Frequent appearance of cartilage islands suggested ischemia and low oxygen tension in the distraction regenerate. We concluded that nicotine compromises bone regeneration possibly by causing ischemia and directly inhibitory effect on osteoblastic cells. Nicotine exposure enhances angiogenesis but cannot compensate for the adverse effect of vasoconstriction.
尼古丁是香烟中导致烟草产生病理效应的主要化学物质。尼古丁对骨愈合的影响仍存在争议。牵张成骨为研究骨愈合和再生提供了一个理想模型。本研究旨在使用下颌骨延长的兔模型评估尼古丁对血液灌注、血管生成和骨形成的影响。将20只成年新西兰白兔随机分为对照组和尼古丁组。所有动物的尼古丁或安慰剂总暴露时间为7周。在截骨术后2周或4周的巩固期、3天的延迟期和11天的主动牵张后，处死动物并获取下颌骨。分别通过激光多普勒监测和IV型胶原免疫组织化学染色评估血液灌注和血管化。通过放射学、组织学和免疫组织化学检查评估骨形成。结果显示，暴露于尼古丁增加了微血管密度，然而却抑制了血流和骨形成。成骨细胞中骨形态发生蛋白（BMP）-2的表达也降低。软骨岛的频繁出现提示牵张再生区存在缺血和低氧张力。我们得出结论，尼古丁可能通过导致缺血以及对成骨细胞的直接抑制作用损害骨再生。暴露于尼古丁可增强血管生成，但无法补偿血管收缩的不利影响。
