Upregulation of VEGF in subchondral bone of necrotic femoral heads in rabbits with use of extracorporeal shock waves
Upregulation of VEGF in subchondral bone of necrotic femoral heads in rabbits with use of extracorporeal shock waves
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体外冲击波上调兔股骨头坏死软骨下骨中的 VEGF
DOI：
10.1007/s00223-007-9046-9
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发表时间：
2007-08-01
影响因子：
4.2
通讯作者：
Li, Xiao-Lin
中科院分区：
文献类型：
--
作者：
Ma, Huan-Zhi;Zeng, Bing-Fang;Li, Xiao-Lin
体外冲击波治疗股骨头缺血性坏死似乎是有效的。然而，生物事件的途径，从而实现这一点还没有完全阐明。本研究旨在探讨体外冲击波对兔坏死股骨头血管内皮生长因子（VEGF）表达的影响。通过免疫组化、实时定量PCR和Western印迹分析评估VEGF表达。还评估了血管生成的程度，如通过微血管密度（MVD）确定的，其评估基于表达CD31的血管。用甲泼尼龙和脂多糖诱发30只新西兰兔双侧股骨头缺血性坏死。左侧肢体（研究侧）接受股骨头冲击波治疗。右侧肢体（对照侧）未接受冲击波治疗。在第1、2、4、8和12周进行股骨头活检。Western印迹分析和实时荧光定量PCR显示，冲击波治疗显着增加VEGF蛋白和mRNA的表达，分别在治疗的坏死股骨头的软骨下骨。与对照组相比，VEGFmRNA表达水平在冲击波处理后2周达到高峰，并持续8周，然后在12周下降，而VEGF蛋白表达水平在冲击波处理后4周达到高峰，并持续12周。对照组血管内皮生长因子的免疫染色较弱，冲击波治疗组的免疫反应水平在4周时增加，并持续12周。在坏死区上方的增殖区中观察到最强的VEGF免疫反应性。在冲击波治疗后4、8、12周，治疗组股骨头软骨下骨的MVD显著高于未治疗组股骨头软骨下骨。这些数据清楚地表明，体外冲击波可以显着上调VEGF的表达。VEGF的上调可能在诱导新生血管长入和改善股骨头血供中起作用。
Extracorporeal shock wave treatment appears to be effective in patients with avascular necrosis of the femoral head. However, the pathway of biological events whereby this is accomplished has not been fully elucidated. The purpose of this study was to investigate the effect of extracorporeal shock waves on vascular endothelial growth factor (VEGF) expression in necrotic femoral heads of rabbits. VEGF expression was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot analysis. The degree of angiogenesis was also assessed, as determined by the microvessel density (MVD), the assessment of which was based on CD31-expressing vessels. Bilateral avascular necrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in 30 New Zealand rabbits. The left limb (the study side) received shock wave therapy to the femoral head. The right limb (the control side) received no shock wave therapy. Biopsies of the femoral heads were performed at 1, 2, 4, 8, and 12 weeks. Western blot analysis and real-time PCR showed that shock wave therapy significantly increased VEGF protein and mRNA expression, respectively, in the subchondral bone of the treated necrotic femoral heads. Compared with the contralateral control without shock wave treatment, the VEGF mRNA expression levels increased to a peak at 2 weeks after the shock wave treatment and remained high for 8 weeks, then declined at 12 weeks, whereas the VEGF protein expression levels increased to a peak at 4 weeks after the shock wave treatment and remained high for 12 weeks. The immunostaining of VEGF was weak in the control group, and the immunoreactivity level in the shock-wave-treated group increased at 4 weeks and persisted for 12 weeks. The most intensive VEGF immunoreactivity was observed in the proliferative zone above the necrotic zone. At 4, 8, and 12 weeks after the shock wave treatment, MVD in subchondral bone from treated femoral heads was significantly higher than that in subchondral bone from untreated femoral heads. These data clearly show that extracorporeal shock waves can significantly upregulate the expression of VEGF. The upregulation of VEGF may play a role in inducing the ingrowth of neovascularization and in improving the blood supply to the femoral head.