经鼻给予VEGF治疗脑缺血/再灌注大鼠的量效关系

目的探讨经鼻给予血管内皮生长因子(VEGF)治疗脑缺血/再灌注损伤大鼠的量效关系。方法48只SD大鼠随机分为四组:低剂量组(100μg/mL)、中剂量组(200μg/mL)、高剂量组(500μg/mL)及盐水对照组(n=12)。通过阻塞大脑中动脉制作大鼠局灶性脑缺血90 m in再灌注损伤模型。缺血后1d、7d和14 d行神经功能评价,14 d动物被麻醉,行组织学检查,应用图像分析系统计算梗死体积、评价血管形成。结果与对照组相比,经鼻给予中剂量VEGF,可明显降低梗死体积,改善神经功能(P<0.01);而低和高剂量组对比于对照组,不能降低脑缺血后大鼠脑梗死体积和改善神经功能(P>0.05)。与对照组相比,经鼻给予中和高剂量VEGF,可增加缺血后脑表面血管形成(P<0.01);而低剂量组对比于对照组,不能促进脑缺血后血管生成(P>0.05)。结论经鼻给予中剂量VEGF可有效降低脑缺血/再灌注损伤大鼠梗死体积,改善神经功能,增加血管密度。因此经鼻给予中等剂量(200μg/mL)VEGF是治疗脑缺血/再灌注损伤的最佳剂量,其可用于进一步评价VEGF作用的有效实验剂量。

The dose-effectiveness of intranasal VEGF in focal cerebral ischemia/reperfusion injury of rats

Objective To study the dose-effectiveness of intranasal （IN） vascular endothelial growth factor （VEGF） in focal cerebral isehemia/reperfusion injury of rats. Methods Sprague-Dawley rats were randomized into four groups as IN low （100 μg/mL）, IN middle （200 μg/mL） and IN high （500 μg/mL） VEGF-treated group, and IN saline-treated group （n = 12 ） , given recombinant human VEGF or saline intranasally. Focal cerebral ischemia/ reperfusion was induced by transient （ 90 minutes ） middle cerebral artery occlusion （ MCAO ） method. Behavioral neurological deficits were assessed 1 d, 7 d and 14 d after the onset of MCAO. Rats were euthanized at 14 d, the brain sections were stained and an image analysis system was used to calculate the infarct volume and calculated the number of cerebral vessels. Results Compared to IN saline, infarct volume after MCAO significantly reduced （P 〈0.01 ） in rats which received the middle （200 μg/mL） dose of IN VEGF. VEGF with middle dose significantly improved behavioral recovery （P 〈 0.01 ）. No significant differences in behavioral recovery and infarct volume after MCAO were seen between the IN saline group and in low and high VEGF-treated group （P 〉 0.05 ）. Compared to IN saline, VEGF with middle and high dose significantly increased the number of cerebral vessels （P 〈0.01 ）. No significant differences in the number of cerebral vessels were seen between the IN saline group and low VEGF-treated group （P 〉 0.05 ）. Conclusion The middle dose （200 μg/mL）of IN VEGF was most effective at reducing infarct volume, improving behavioral recovery and increasing the number of vessels, which can be used in the following treatments to further evaluate the effect of VEGF.