草酸艾司西酞普兰对大鼠脑缺血再灌注损伤的神经保护作用

Neuroprotective effect of escitalopram oxalate on cerebral ischemia reperfusion injury in rats

目的探讨草酸艾司西酞普兰对局灶性脑缺血再灌注大鼠的神经保护作用及可能的机制。方法取SD雄性大鼠160只,随机分为假手术组(Sham组)、生理盐水组(NS组)、干预组(CIT组,又分干预14 d组和21 d组)。线栓法制作大鼠局灶性脑缺血再灌注(MCAO)模型,使用改良神经功能缺损(modified neurological severity score,mNSS)量表评价各组大鼠神经功能缺损情况。分别于术后14 d和21 d按不同的实验时间点,使用激光共聚焦技术观察各组大鼠缺血区微血管直径、密度和总面积。酶联免疫吸附法检测血浆血管内皮生长因子(VEGF)浓度。免疫组化染色法和蛋白质印迹法检测VEGF表达。结果模型制作后,干预14 d组和干预21 d组内的大鼠神经功能缺损情况明显改善,各项指标检测结果如下:术后14 d mNSS评分,生理盐水组评分为(6.57±1.13)分,干预14 d组评分为(4.39±0.92)分,较生理盐水组明显降低(P<0.05);术后21 d mNSS评分,干预21 d组[(3.23±0.55)分]较干预14 d组[(4.14±0.74)分]明显降低(P<0.01)。术后14 d三维共聚焦结果显示:药物干预的效果随着时间的推移而逐步见效。术后14 d酶联免疫吸附法结果显示:相对于假手术组、生理盐水组干预14 d组和干预21 d组血浆VEGF浓度显著增加,药物干预后的实验组VEGF蛋白水平可显著增高。术后14 d免疫组化分析法显示:干预21 d组缺血脑组织VEGF表达显著性高于干预14 d组(P<0.01)。结论草酸艾司西酞普兰可以明显减轻脑缺血再灌注大鼠的神经损伤和改善神经功能,具有神经保护作用,且药物干预的效果随着时间的推移而逐步增强,其机制可能与VEGF介导的血管新生有关。

Objective To explore neuroprotective effect of escitalopram oxalate on cerebral ischemia reperfusion in injury rats and its possible mechanism,thus provide experimental evidence for the use of the drug in the clinical treatment of ischemic cerebrovascular disease.Methods 160 male rats of SD were selected and randomly divided into three groups:sham operation group(Sham group),negative control group(NS group),intervention group(CIT group,for 14 days and 21 days).Focal middle cerebral artery occlusion model(MCAO)of rats were constructed.Neurological deficit of rats in each group were evaluated by modified neurological severity score(mNSS)scale.Microvessel diameter,density,and total area of each group angiogenesis in cerebral ischemic area were observed by Laser cofocal technology after 14 days and 21 days at different time points;the plasma concentrations of VEGF were detected by ELASA,and expression levels of VEGF were detected by immunohistochemical assay and Western blot in each group,to explore its possible mechanism of molecular biology.Results After modeling,neurological deficit of intervention group for 14 days and 21 days were improved significantly.The indicators were as follows:scores of mNSS in NS group(6.57 ±1.13)was significantly higher than(4.39 ±0.92)in intervention group for 14 days(P<0.05);scores of mNSS in intervention group(3.23 ±0.55)for 21 days was significantly lower than(4.14 ±0.74)in intervention group for 14 days(P<0.01).Confocal 3D imaging results after 14 days showed:microvascular total area was significantly lager which illustrated that the effect of drug intervention for 14 days started to work over time.Plasma concentrations and expression levels of VEGF in intervention group for 14 days and 21 days were higher than those in Sham group,NS group.VEGF protein expression of cerebral ischemia tissues in intervention group for 21 days were higher than that of 14 days(P<0.01).Conclusion Escitalopram oxalate could significantly reduce cerebral ischemia and reperfusion in rats nerve injury and improve neurological function,which has a neuroprotective effect,the effect of drug intervention gradually increases over time,and the possible mechanism of which is related to angiogenesis mediated by VEGF.