夏天无调控VEGF/VEGFR2通路改善VD大鼠学习记忆能力的机制研究

Mechanism of Xiatianwu(夏天无)Improving Learning and Memory Ability in VD Rats through the VEGF/VEGFR2 Pathway

目的:基于VEGF/VEGFR2通路探讨夏天无改善血管性痴呆大鼠学习记忆的相关作用机制。方法:选取10 w~12 w龄清洁级健康雄性SD大鼠,采用改良双侧颈总动脉结扎(2-VO)法制备VD动物模型,随机分为:模型对照组、尼莫地平0.01 g/kg组及夏天无0.2、0.4、0.8 g/kg组,另设假手术对照组。连续灌胃40 d后,通过Morris水迷宫观察各组大鼠神经行为学差异,HE染色观察其病理改变,免疫组织化学法检测CD34、VEGF及VEGFR2的蛋白阳性表达变化。结果:与假手术对照组比较,模型对照组大鼠学习记忆能力明显降低,相关皮质及海马区内神经细胞均存在不同程度的病理损伤,VEGF及VEGFR2阳性表达增强,微血管密度增大(P<0.01);与模型对照组比较,各治疗组学习记忆能力均明显提高(P<0.05或P<0.01),神经细胞损伤得到不同程度改善,CD34、VEGF及VEGFR2阳性表达明显增强(P<0.05或P<0.01),微血管密度明显增大(P<0.05或P<0.01)。结论:夏天无一定程度上可改善血管性痴呆大鼠学习记忆能力,其机制可能与增强脑组织内VEGF及VEGFR2蛋白表达,增大微血管密度,改善血液供应,从而增强对神经元的保护作用有关。

Objective:To explore the underlying mechanism of Xiatianwu(夏天无)in improving learning and memory ability of vascular dementia(VD)rats based on the vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor-2(VEGFR2)pathway.Methods:Clean male healthy SD rats(10–12 weeks old)were selected and the modified bilateral common carotid artery ligation(2-VO)method was used to induce VD in rats.Then rats were randomized into sham operation group,model control group,Nimodipine(0.01 g/kg)group,and Xiatianwu(0.2 g/kg,0.4 g/kg,0.8 g/kg)groups.After continuous gavage for 40 days,the Morris water maze was used to observe the neurobehavioral differences in each group.Based on hematoxylin and eosin(HE)staining,the pathological changes were observed,and immunohistochemistry was employed to detect the protein expression of cluster of differentiation 34(CD34),VEGF,and VEGFR2.Results:Compared with sham operation group,the model control group showed low learning and memory ability,pathological injury in the neurons in cortex and hippocampus tissue,high expression of VEGF and VEGFR2,and high density of microvessels(P<0.01).Compared with the model control group,the treatment groups demonstrated high learning and memory ability(P<0.05,P<0.01),alleviation of neuron damage,high expression of CD34,VEGF,and VEGFR2(P<0.05,P<0.01),and high microvessel density(P<0.05,P<0.01).Conclusion:Xiatianwu can improve the learning and memory ability of VD rats.The mechanism is the likelihood that it enhances the expression of VEGF and VEGFR2 proteins in the brain,increases the density of microvessels,and improves blood supply,thereby enhancing the protective effect on neurons.