电针对血管性认知障碍大鼠学习记忆与海马内血管内皮生长因子及其受体1、2 mRNA表达的影响

目的:探讨电针对血管性认知障碍大鼠学习记忆及海马内血管内皮生长因子(VEGF)及其受体1(VEGFR-1/Flt-1)、受体2(VEGFR-2/Flk-1)mRNA表达的影响,为临床治疗血管性认知障碍提供理论和实验依据。方法:Wistar大鼠60只,随机选取12只作为假手术组,其余大鼠采用改良的四血管阻断法进行血管性认知障碍模型复制,将模型复制成功的大鼠保留36只,随机分为模型对照组、电针治疗组和西药治疗组,每组12只。电针治疗组大鼠电针"大椎""百会""水沟""神庭"穴,西药治疗组予茴拉西坦0.0625g/kg灌胃,均1次/d,10次为1个疗程,共治疗2个疗程。采用跳台实验测试各组大鼠学习记忆成绩,测定各组大鼠的神经行为学评分,RT-PCR法检测大鼠海马VEGF、Flt-1、Flk-1mRNA的表达。结果:模型对照组大鼠学习成绩表现为反应时间延长、错误次数增多,记忆成绩表现为潜伏时间缩短、错误次数增多,神经行为学评分显著升高,海马内VEGF、Flt-1、Flk-1 mRNA表达增强,与假手术组比较差异有统计学意义(均P0.01);电针治疗组大鼠学习记忆成绩改善明显,神经行为学评分显著降低,海马内VEGF、Flt-1、Flk-1mRNA表达明显增强,与模型对照组比较,差异有统计学意义(均P0.01)。电针治疗组大鼠学习成绩、神经行为学评分、海马内VEGF mRNA及Flt-1 mRNA与西药治疗组比较差异亦有统计学意义(均P0.05)。结论:电针能显著提高血管性认知障碍大鼠学习记忆成绩,上调海马内VEGF、Flt-1、Flk-1mRNA的表达,促进了要害部位的血管生成,可能是其治疗血管性认知障碍的重要作用机制之一。

Effects of Electroacupuncture on Learning-memory Ability and Expression of Hippocampal Vascular Endothelial Growth Factor(VEGF),VEGF Receptor 1 and 2 Genes in Vascular Cognitive Impairment Rats

Objective To observe the effect of electroacupuncture(EA)of"Dazhui"(GV 14),"Baihui"(GV 20),etc.on learning-memory ability and expression of vascular endothelial growth factor(VEGF)mRNA,VEGF receptor 1(VEGFR-1/Flt-1)mRNA,and VEGFR-2(Flk-1)mRNA in the hippocampus in vascular cognitive impairment(VCI)rats so as to reveal its mechanism underlying improvement of VCI.Methods A total of 60 Wistar rats were randomly divided into sham operation,VCI model,EA and medication groups(n=12in each group).The VCI model was established by occlusion of the bilateral vertebral arteries and bilateral cervical arteries.EA(2Hz/20Hz)was applied to"Baihui"(GV 20),"Dazhui"(GV 14),"Shuigou"(GV 26)and"Shenting"(GV 24)for 20 min,once daily for 20 days.Rats of the medication group were treated by intragastric perfusion of Aniracetam capsules(0.0625g/kg),once daily for 20 days.The rats' learning-memory ability was detected by step-down test.The expression levels of VEGF mRNA,Flt-1mRNA and Flk-1mRNA in the hippocampus were detected by RT-PCR,and the neurological deficit scores were assessed by Zea Longa(0-4scaling)method.Results Compared with the sham operation group,rats of the model group showed a significant increase in reaction time and error number and decrease of escape latency(reduction of learning-memory ability),and increase in neurological deficit score,and in expression levels of hippocampal VEGF mRNA,Flt-1mRNA and Flk-1mRNA(all P<0.01).After EA treatment,in comparison with the model group,the learning-memory ability and hippocampal VEGF mRNA,Flt-1mRNA and Flk-1mRNA were apparently increased,neurological deficit score were markedly decreased in the EA group(all P<0.01).The effects of EA treatment was obviously superior to those of medication in raising learning-memory ability and up-regulating hippocampal VEGF mRNA and Flt-1mRNA expression levels,and in reducing neurological deficit score(all P<0.05).Conclusion EA intervention can apparently up-regulate hippocampal VEGF mRNA,Flt-1mRNA and Flk-1mRNA expression in VCI rats,which may contribute to its effect in improving learning-memory ability,possibly by promoting neovasculization.