Vascular Endothelial Growth Factor in Rabbits During Development of Corticosteroid-Induced Osteonecrosis: A Controlled Experiment
Vascular Endothelial Growth Factor in Rabbits During Development of Corticosteroid-Induced Osteonecrosis: A Controlled Experiment
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DOI：
10.3899/jrheum.070838
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发表时间：
2008-12-01
影响因子：
3.9
通讯作者：
Tomita, Katsuro
中科院分区：
文献类型：
--
作者：
Kabata, Tamon;Matsumoto, Tadami;Tomita, Katsuro
目标。血管内皮细胞生长因子(VEGF)是血管生成启动子中的一种，是对局部缺氧的快速反应。我们在一项对照实验中研究了兔血管内皮生长因子的表达，以阐明皮质类固醇诱导的骨坏死(ON)中缺血事件的发生。成年日本大耳白兔99只，随机分为6个处理组和一个未处理对照组。治疗组一次性肌肉注射4 C甲基强的松龙4 mg/kg，不同时间安乐死，取股骨组织标本。我们通过组织病理学、免疫组织化学、Northern印迹分析和Western印迹分析来检测ON的发生和VEGF的表达。组织病理学检查，最早出现ON指征是在皮质激素治疗后5天。ON的发生频率在1周或以后达到高峰，VEGF的表达伴随着ON的发展。免疫组织化学检测发现，在骨髓细胞中可见血管内皮生长因子阳性细胞，且多位于血管内皮细胞周围，提示血管内皮细胞生长因子的产生是由血管内皮细胞缺血事件引起的。Northern印迹分析显示，皮质类固醇治疗后3d，血管内皮细胞生长因子-mRNA表达水平达到高峰，7d后逐渐下降至对照组水平。免疫印迹分析显示皮质类固醇治疗后3d有血管内皮生长因子蛋白表达。糖皮质激素治疗2周或更长时间后，血管内皮生长因子表达水平与对照组基本相同。我们观察了早期糖皮质激素诱导的兔皮损周围细胞中血管内皮生长因子的表达。这些结果表明，导致ON的缺血事件在最初的皮质类固醇治疗后不久就开始了。(2008年11月1日首次发布；J Rheumatol 2008年；35：2383-90；DOI：10.3899/jrangum.070838)
Objective. Vascular endothelial growth factor (VEGF) is in angiogenic promoter that is rapidly induced as a response to local hypoxia. We investigated VEGF expression in rabbits in a controlled experiment to clarify the onset of ischemic events in corticosteroid-induced osteonecrosis (ON).Methods. Ninety-nine mature Japanese white rabbits were divided into 6 treatment groups and an untreated control group. The treatment groups received a single intramuscular injection of 4 mg/kg 4 C methylprednisolone acetate; they were euthanized at different times, and tissue samples were obtained from their femora. We examined the development of ON and the expression of VEGF using histopathology, immunohistochemistry, Northern blot analysis, and Western blot analysis.Results. On histopathological examination, the earliest indication of ON was 5 days after the corticosteroid treatment. The frequency of ON occurrence reached a plateau at or after Week 1. VEGF expression was accompanied by the development of ON. VEGF-positive cells detected by immunohistochemistry were found among bone marrow cells, frequently located in the area surrounding ON, suggesting that VEGF production was switched on as a result of the ischemic events that cause ON. The level of VEGF-mRNA expression indicated by Northern blot analysis peaked at 3 days after the corticosteroid treatment and decreased gradually to the levels present in the control group at 7 days after treatment. Western blot analysis revealed VEGF protein production at 3 days after the corticosteroid treatments. Levels of VEGF expression 2 weeks or more after the corticosteroid treatment were almost the same as in the control group.Conclusion. We observed early expression of VEGF in the cells around the corticosteroid-induced ON lesions in rabbits. These results suggest that the ischemic events that cause ON begin soon after the initial corticosteroid treatment. (First Release Nov 1 2008; J Rheumatol 2008;35:2383-90; doi: 10.3899/jrheum.070838)