Yang Ji-Ping, Liu Huai-Jun, Wang Zhao-Lu, Cheng Song-Ming, Cheng Xi, Xu Ge-Lin, Liu Xin-Feng
Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Neurosci Lett. 2009 Sep 25;461(3):212-6. doi: 10.1016/j.neulet.2009.06.060. Epub 2009 Jun 24.
The aim of the present study was to assess the dose-effectiveness of intranasal (IN) vascular endothelial growth factor (VEGF)in the treatment of experimental stroke. Sprague-Dawley rats were randomized into four groups as IN low (100 microg/ml), IN middle (200 microg/ml) and IN high (500 microg/ml) VEGF-treated group, and IN saline-treated group (n=12), given recombinant human VEGF 165 or saline intranasally. Focal cerebral ischemia was induced by transient (90 min) middle cerebral artery occlusion (MCAO) method. Behavioral neurological deficits were assessed 1, 7 and 14 d after the onset of MCAO. Rats were sacrificed at 14 d, the brain sections were stained and an image analysis system was used to calculate the infarct volume. Microvessels were labeled by FITC-dextran and the segment lengths, diameters and number of microvessels were measured by Image Pro-Plus Version 6.0 software. Fourteen days post MCAO, infarct volume significantly reduced (P<0.01) in rats which received the middle dose of IN VEGF when compared to IN saline. And middle dose of VEGF significantly improved behavioral recovery (P<0.01). No significant difference in the behavioral recovery and infarct volume was observed between the saline-treated group and the low or high VEGF-treated groups (P>0.05). Compared to IN saline, middle and high doses of VEGF significantly increased the segment length, diameter and number of microvessels (P<0.01). No significant difference in the segment length, diameter and number of microvessels was observed between the IN saline-treated group and the low VEGF-treated group (P>0.05). The middle dose of IN VEGF was most effective on reducing infarct volume, improving behavioral recovery and enhancing angiogenesis in stroke brain, which can be used in the following treatments to further evaluate the effect of VEGF.
本研究的目的是评估鼻内（IN）血管内皮生长因子（VEGF）治疗实验性中风的剂量有效性。将Sprague-Dawley大鼠随机分为四组，即低剂量（100微克/毫升）、中剂量（200微克/毫升）和高剂量（500微克/毫升）IN VEGF治疗组以及IN生理盐水治疗组（n = 12），通过鼻内给予重组人VEGF 165或生理盐水。采用短暂（90分钟）大脑中动脉闭塞（MCAO）法诱导局灶性脑缺血。在MCAO发作后1、7和14天评估行为神经功能缺损。14天时处死大鼠，对脑切片进行染色，并使用图像分析系统计算梗死体积。用异硫氰酸荧光素标记的葡聚糖标记微血管，并用Image Pro-Plus 6.0版软件测量微血管的节段长度、直径和数量。MCAO后14天，与IN生理盐水组相比，接受中剂量IN VEGF的大鼠梗死体积显著减小（P<0.01）。中剂量VEGF显著改善了行为恢复（P<0.01）。生理盐水治疗组与低剂量或高剂量VEGF治疗组在行为恢复和梗死体积方面未观察到显著差异（P>0.05）。与IN生理盐水相比，中剂量和高剂量VEGF显著增加了微血管的节段长度、直径和数量（P<0.01）。IN生理盐水治疗组与低剂量VEGF治疗组在微血管的节段长度、直径和数量方面未观察到显著差异（P>0.05）。中剂量的IN VEGF在减少梗死体积、改善行为恢复和促进中风脑内血管生成方面最有效，可用于后续治疗以进一步评估VEGF的效果。
