表达hVEGF165重组腺相关病毒对脊髓损伤的作用

血管内皮细胞因子曾经被认为是具有促血管生成作用的血管生长因子，如今，更多的研究将其应用于神经细胞缺血损伤的保护中。然而，一些研究却认为VEGF的应用使得脊髓损伤后脊髓的二次打击更加严重。为了探讨VEGF是否能够有效保护损伤的脊髓，我们在大鼠脊髓损伤模型中应用了表达hVEGF165的重组腺相关病毒。我们将大鼠随机分为假手术组，单纯脊髓损伤对照组，AAV-GFP组及AAV-VEGF 组。在相应时间点评估完神经功能后，我们将脊髓组织迅速取出。我们通过透射电子显微镜观察及TUNEl凋亡组织学染色观察在形态学角度评估凋亡的发生。应用免疫组化及Western blot评估凋亡蛋白Bax 和Bcl-2的表达。通过水通道蛋白-4（AQP-4）的免疫组化染色观察VEGF表达与脊髓损伤的相关性。实验结果显示，AAV-VEGF 组神经功能较对照组及AAV-GFP组有显著差异。(P < 0.05). VEGF能够明显抑制神经细胞的凋亡，减少运动神经元的损伤和丢失，减少细胞凋亡率。VEGF治疗组BAX蛋白表达减弱，Bcl-2蛋白表达加强，AQP-4表达减弱。所有结果表明VEGF具有对脊髓损伤神经的保护效应。

Effects of recombinant adeno-associated viruses expressing human vascular endothelial growth factor 165 on spinal cord injury

Numerous studies have confirmed that vascular endothelial growth factor (VEGF) improves the function of neural cells following spinal cord injury (SCI). However, some studies have also verified that VEGF cannot significantly induce the increase in vascular density at or surrounding the lesion, and that VEGF therapy exacerbated secondary damage following SCI. Based on the dual effects of VEGF on SCI, we constructed the recombinant adeno-associated viruses (rAAV)-hVEGF165-IRES-human recombinant green fluorescent protein (hrGFP) (AAV-VEGF) and rAAV-IRES-hrGFP (AAV-GFP). Our results suggested that rAAV expressed hVEGF165, and a low dose of VEGF relieved increased vascular permeability, improved microcirculation in the local spinal cord, lessened spinal cord edema, and decreased neuronal apoptosis. These results verified that the releasing effects of the rAAV virus vector had protective effects on the spinal cord.