补肾活血方对血管性痴呆大鼠脑海马脑源性神经生长因子介导的PI3K/AKT信号通路的影响  

The Effect of Bushenhuoxue Prescription on the PI3-K/AKT Signal Pathway Mediated by BDNF in Hippocampus of Vascular Dementia Rats

作　　者：于文涛[1,2] 赵润生 高维娟[1,2] 王香婷 张卫民[1] 徐华洲 Yu Wentao;Zhao Runsheng;Gao Weijuan;Wang Xiangting;Zhang Weimin;Xu Huazhou(Hebei University of Chinese Medicine,Shijiazhuang 050200;Hebei Key laboratory of Chinese medicine disease,shijiazhuang 050091)

机构地区：[1]河北中医学院,石家庄050200 [2]河北省心脑血管病中医药防治重点实验室,石家庄050091

出　　处：《中药药理与临床》2018年第3期141-146,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：河北省自然科学基金资助项目(NO:H2015423057)

摘　　要：目的:从脑源性神经生长因子(BDNF)介导的PI3K/AKT信号通路角度探讨补肾活血方对血管性痴呆(VD)大鼠脑海马经元保护机制。方法:将70只SD大鼠随机分为假手术组14只、模型组14只、补肾活血方组(10.14g/kg、5.07g/kg)28只、尼莫地平组(0.011g/kg)14只,除假手术组外,采用两血管阻断法制备大鼠VD模型,药物组分别以10.14g/kg和5.07g/kg灌服补肾活血方药液,阳性组以0.011g/kg灌服尼莫地平药液,假手术组、模型组均以10ml/kg体重灌服生理盐水,每日1次,给药30d天后,采用透射电子显微镜观察各组大鼠脑海马神经元超微结构变化;Tunel法检测细胞凋亡变化;采用实时荧光定量PCR(RT-q PCR)和Western-blot检测海马组织BDNF、酪氨酸蛋白激酶B(Trk B)、磷脂酰肌醇3激酶(PI3-K)、丝氨酸-苏氨酸激酶(AKT)蛋白及基因表达的变化。结果:与假手术组比较,模型组大鼠脑海马组织BDNF、Trk B、PI3-K、AKT蛋白及基因表达水平均呈显著下降,脑海马神经元超微结构明显受损,细胞凋亡平均光度值显著升高,平均灰度值显著下降;与模型组比较,补肾活血方10.14g/kg和5.07g/kg剂量组均能显著提高脑海马组织BDNF、Trk B、PI3-K、AKT蛋白及基因表达,改善脑海马神经元超微结构,细胞凋亡平均光度值显著下降,平均灰度值显著升高。结论:补肾活血方可通过调控BDNF介导的PI3-K/AKT信号通路,发挥神经元保护作用。Objective： To probe the protection mechanism of bushenhuoxue prescription on hippo-campal neurons by regulating the PI3-K/AKT signal pathway mediated by Brain-derived neurotrophic factor（BDNF） of vascular dementia rats. Methods： The 70 SD rats were randomly divided into 14 sham operation group,14 model group,28 Bushenhuoxue prescription group（10. 14 g/kg and 5. 07 g/kg） and 14 Nimodipine group（0. 011 g/kg）. The model rats of vascular dementia were reproducted by blocking both-blood vessel except sham operation group. The different Bushenhuoxue prescription group was administered with 10. 14 and 5. 07 g/kg body weight respectively. Nimodipine was administered with 0. 011 g/kg body weight. The sham operation group and model group were fed with saline at 10 ml/kg,once a day. After 30 days,the ultramicrostructure of hippocampal neuron were observed by transmission electron microscope,change of cell apoptosis were observed by Tunel method,the expression of BDNF,tyrosine protein kinase B（Trk B）,phosphatidyl inositol 3 kinase（PI3-K） and serine/threonine kinase（AKT） of VD rats were observed in protein and gene level by RT-q PCR and Western-blot. Results： Compared with sham operation group,the expression of BDNF,Tr KB,PI3-K and AKT in hippocampal tissue of VD model rats was decreased in gene and proteinum level（P〈0.05）,and the ultramicrostructure of hippocampal neuron were damaged,The average luminance of cell apoptosis were increaced,and the average gray scale were decreaced（P〈0. 01）. Compared with model group,the expression of BDNF,Tr KB,PI3-K and AKT in hippocampal tissue was increased in gene and protein level（P〈0. 05）,and the ultramicrostructure of hippocampal neuron were improved,the average luminance of cell apoptosis were decreaced,and the average gray scale were increased in the bushenhuoxue prescription group（10. 14 g/kg and 5.07 g/kg,P〈0. 01）. Conclusion： The bushenhuoxue prescription could regulate PI3-K/AKT signal pathway mediated by BDNF,so as to protec

关 键 词：补肾活血方 血管性痴呆 脑源性神经生长因子 酪氨酸蛋白激酶B PI3-K/AKT信号通路 超微结构 

分 类 号：R285.5[医药卫生—中药学]