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目的探讨血管内皮生长因子(VEGF)对兔脑缺血再灌注损伤半胱氨酸蛋白酶(caspase)-3、-9、-12和c-jun的影响,从多角度探讨VEGF介导神经保护作用的调控机制。方法健康雄性新西兰白兔26只,体重2.6±0.2kg。随机分成假手术组(Sham组,n=6)、缺血/再灌注损伤组(I/R组,n=10)和VEGF治疗组(V组)(n=10)。实验3d后,各组行神经功能缺损评分、TTC染色测梗死体积、免疫组织化学方法检测缺血半暗带区caspase-3、-9、-12和c-jun表达、用DNA原位末端缺口标记法(TUNEL法)检测相应区域的神经细胞凋亡。结果Sham组未见梗死体积及神经功能缺损,caspase-3、-9、-12和c-jun呈低表达,TUNEL染色见少量阳性细胞;与Sham组比较,I/R组和V组可见左侧半球梗死,神经功能缺损,caspase-3、-9、-12和c-jun表达增加(I/R组:0.49±0.05、0.38±0.02、0.36±0.02、0.37±0.04;V组:0.24±0.05、0.18±0.02、0.15±0.03、0.17±0.03;Sham组:0.09±0.03、0.08±0.03、0.07±0.02、0.08±0.02,P<0.01),TUNEL阳性细胞数增多(32.8±2.6,9.3±0.9 vs.0.7±0.2,P<0.01);与I/R组比较,V组梗死体积减少(367.0±15.7)mm3 vs.468.6±29.7mm3,P<0.01),神经功能恢复更好,caspase-3、-9、-12和c-jun表达明显下降(0.24±0.05、0.18±0.02、0.15±0.03、0.17±0.03 vs.0.49±0.05、0.38±0.02、0.36±0.02、0.37±0.04,P<0.01),TUNEL阳性细胞数明显减少(32.8±2.6 vs.9.3±0.9,P<0.01)。结论VEGF可通过下调凋亡基因的表达,抑制反应性凋亡途径的激活来发挥其神经保护作用。
Objective To investigate the effect of vascular endothelial growth factor (VEGF) on the expression of caspase-3, -9, -12 and c-jun after cerebral ischemia-reperfusion in rabbits and to explore the neuroprotective effects of VEGF mediated by VEGF The regulatory mechanism. Methods Twenty-six healthy male New Zealand white rabbits, weighing 2.6 ± 0.2 kg. The rats in Sham group (n = 6), ischemia / reperfusion injury group (n = 10) and VEGF treatment group (n = 10) were randomly divided into three groups. After 3 days of experiment, neurological deficit score, TTC staining were used to measure the infarct volume. The expression of caspase-3, -9, -12 and c-jun in ischemic penumbra was detected by immunohistochemical method. TUNEL method was used to detect neuronal apoptosis in the corresponding area. Results There was no infarction volume and neurological deficit in Sham group, while the expression of caspase-3, -9, -12 and c-jun was low, and TUNEL staining showed few positive cells. Compared with Sham group, I / R and V group showed left There was an increase in the expression of caspase-3, -9, -12 and c-jun in the hemispheric infarcts and neurological deficits (I / R group: 0.49 ± 0.05,0.38 ± 0.02,0.36 ± 0.02,0.37 ± 0.04; 0.05,0.18 ± 0.02,0.15 ± 0.03,0.17 ± 0.03; Sham group: 0.09 ± 0.03,0.08 ± 0.03,0.07 ± 0.02,0.08 ± 0.02, P <0.01), the number of TUNEL positive cells increased (32.8 ± 2.6,9.3 ± 0.9 vs.0.7 ± 0.2, P <0.01) .Compared with I / R group, the volume of infarction in V group decreased (367.0 ± 15.7) mm3 vs.468.6 ± 29.7 mm3, P <0.01) 3, -9, -12 and c-jun were significantly decreased (0.24 ± 0.05,0.18 ± 0.02,0.15 ± 0.03,0.17 ± 0.03 vs.0.49 ± 0.05,0.38 ± 0.02,0.36 ± 0.02,0.37 ± 0.04, P < 0.01). The number of TUNEL positive cells decreased significantly (32.8 ± 2.6 vs.9.3 ± 0.9, P <0.01). Conclusion VEGF can exert its neuroprotective effect by down-regulating the expression of apoptosis gene and inhibiting the activation of the apoptotic pathway.