胶原靶向的血管内皮细胞生长因子结合胶原支架治疗大鼠脑外伤

Traumatic brain injury (TBI) which damage the structure of the brain finally often result in death and disability. The angiogenesis at the injury site could be an important part of the repair. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor that has been known, takes important actions in tissue healing and regeneration. However, it is hard to maintain a sufficient VEGF concentration in the lesion site. In our previous work, a human VEGF fused with a collagen-binding domain (CBD) could specifically bind to collagen. In the present study, a VEGF delivery systems delivery system was constructed by a collagen scaffolding loaded with CBD-VEGF. We labeled VEGF with a single photon emission computed tomography (SPECT) tracer 125I. Labeled CBD-VEGF and natural VEGF were injected with collagen scaffolding in TBI rats and the in vivo nuclear imaging were compared. We suppose that the CBD could enhance VEGF retention in the lesion site and limit distribution to nonspecific tissues. The therapeutic effects were estimated by ethology score, molecular imaging technology and immunohistochemistry.

脑外伤是危害人类健康及生命的疾病之一，临床死亡率高，后遗症多，迫切需要切实有效的治疗方法。在损伤部位的血管新生是外伤修复的重要部分。血管内皮细胞生长因子(VEGF)是目前发现的最强有力的血管生成因子,在组织的修复和重建过程中发挥着重要作用。然而由于VEGF半衰期短且易随脑脊液飘散，如何使VEGF在损伤局部维持持久有效的浓度是目前要解决的关键问题。我们的前期研究发现，在VEGF基础上以一个CBD多肽结构修饰，行成CBD-VEGF,可使营养因子铆定于胶原表面。本实验中，我们将CBD-VEGF结合在胶原支架表面，再植入大鼠陈旧性脑外伤的损伤空洞中，从而形成精巧的缓释系统。我们将核素125I来标记VEGF，用SPECT行VEGF的活体示踪，比较CBD-VEGF和普通VEGF在局部浓聚及组织分布上区别。同时我们应用行为学评分，分子影像技术及免疫组化来评估CBD-VEGF的治疗效果及机制。

脑外伤是危害人类健康及生命的疾病之一，临床死亡率高，后遗症多，迫切需要切实有效的治疗方法。在损伤部位的血管新生是外伤修复的重要部分。血管内皮细胞生长因子(VEGF)是目前发现的最强有力的血管生成因子,在组织的修复和重建过程中发挥着重要作用。然而由于VEGF半衰期短且易随脑脊液飘散，如何使VEGF在损伤局部维持持久有效的浓度是目前要解决的关键问题。我们的前期研究发现，在VEGF基础上以一个CBD多肽结构修饰，行成CBD-VEGF,可使营养因子铆定于胶原表面。本实验中，我们将CBD-VEGF结合在胶原支架表面，再植入大鼠陈旧性脑外伤的损伤空洞中，从而形成缓释系统。我们将核素131I来标记VEGF，用SPECT行VEGF的活体示踪，比较CBD-VEGF和普通VEGF在局部浓聚及组织分布上区别。结果显示CBD-VEGF与胶原材料联合植入损伤处，可以将尽可能多的VEGF结合在胶原材料表面，并且持续稳定释放，使局部新生血管及血流灌注增多，显著的改善脑外伤的治疗效果。