大鼠脊髓损伤后HIF-1α和VEGF表达的上调及其在血管新生中的意义  

Significance of up-regulation of HIF-1α and VEGF expression in angiogenesis after spinal cord injury in rats

作　　者：钱雷敏[1] 许燕[1] 孙湘兰[1] 张志坚[1] 龚爱华[1] 秦茹娟[1] 温泽锋[1] 姜平[1] 

机构地区：[1]江苏大学医学院,江苏镇江212013

出　　处：《江苏大学学报（医学版）》2007年第3期201-204,I0002,共5页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金资助项目(30570981);江苏省卫生厅科技项目(H200545);江苏省高校自然科学基金资助项目(04KJB310020)

摘　　要：目的:探讨脊髓损伤后神经细胞内缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)表达水平的变化在血管新生中的意义。方法:应用改良Allen重击法损伤大鼠T12脊髓,按伤后存活时间再分为脊髓损伤1 d,3d,7 d,14 d和30 d组。各组动物的脊髓切片经免疫荧光染色后,用荧光显微镜观察HIF-1α,VEGF的表达和分布,对Laminin免疫反应阳性的血管基膜进行图像分析,比较上述各组的血管密度。结果:HIF-1α和VEGF共定位于脊髓前角运动神经元,脊髓损伤局部的免疫荧光强度高于正常脊髓内的荧光强度,在脊髓损伤后第3天,其荧光强度达到高峰。脊髓损伤后Laminin阳性血管主要分布于损伤坏死组织周围并逐渐向坏死组织内生长,血管密度经历由低到高的过程。结论:脊髓损伤后损伤部位残存神经元可能通过表达高HIF-1α诱导VEGF表达增加,后者通过旁分泌模式作用于周围血管内皮细胞以促进内皮细胞增殖和血管再生。Objective： To explore changes of HIF-1α and VEGF expression in neurons and their effect on angiogenesis following spinal cord injury. Methods： Adult Sprague-Dawley rats were divided into two groups randomly ： （ 1 ） Normal control group （ n = 5 ） ; （2） SCI （ spinal cord injury） group （ n = 25 ） , and this group was further randomly subdivided into five subgroups according to the postoperative survival time, i.e. SCI ld group, SCI 3d group, SCI 7d group, SCI 14d group and SCI 30d group. Those animals of SCI groups suffered from weight-dropping SCI operation on T12 spinal cord. The expression of HIF-1α and VEGF were examined using immunofluorescence. The density of the Laminin immunoreactive positive vessels of six groups was compared. Results： HIF-1α and VEGF were co-expressed in motoneurons. Their fluorescence intensity at SCI lesion was stronger than that at normal spinal cord, and achieved the top level 3 clays after SCI operation. Laminin positive vessels were mainly distributed in the periphery regions of spinal cord lesion, and gradually increased and grew into the central necrotic tissue. Conclusion： At SCI lesion, those undamaged motoneurons may produce more VEGF through the induction of over-expressed HIF-1α, which continued to react with the surrounding vascular endothelial cells at the manner of paracrine to promote cell proliferation and angiogenesis.

关 键 词：脊髓损伤 缺氧诱导因子-1Α 血管内皮生长因子 血管新生 免疫荧光 大鼠 

分 类 号：R681.5[医药卫生—骨科学]