益气活血中药脑络欣通促进脑缺血气虚血瘀证大鼠脑血管再生及机制  

Mechanisms of Yiqihuoxue herb Naoluoxintong promotes cerebral vascular regeneration in rats with cerebral ischemia syndrome of Qi deficiency accompanied by blood stasis

作　　者：谭辉[1] 尹婷婷[1] 邓勇[1] 何玲[1] 李凤[1] 王玉凤[1] TAN Hui;YIN Tingting;DENG Yong;HE Ling;LI Feng;WANG Yufeng(Ministry-of-Education Key Laboratory of Xin’an Medicine,Anhui University of Chinese Medicine,Hefei 230012,China)

机构地区：[1]安徽中医药大学新安医学教育部重点实验室,安徽合肥230012

出　　处：《细胞与分子免疫学杂志》2020年第8期712-718,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81603523);安徽高校人文社会科学研究重点项目(SK2019A0229)。

摘　　要：目的探讨脑络欣通对大脑中动脉闭塞缺血再灌注(MCAO-R)气虚血瘀证大鼠脑血管再生的影响及其可能机制。方法随机数字表法将SD大鼠分为正常对照组、模型组、脑络欣通高剂量组[1200 mg/(kg·d)]、脑络欣通中剂量组[800 mg/(kg·d)]、脑络欣通低剂量组[400 mg/(kg·d)],各12只,改良线栓法结合多因素复合模拟建立MCAO-R气虚血瘀证模型。根据模型生物学特征评分量化标准进行神经功能缺损、气虚证和血瘀证评分,运用激光多普勒仪动态监测局部脑血流量(rCBF),HE染色观察缺血脑组织病理变化,实时荧光定量PCR检测缺血脑组织Wnt5a、糖原合成酶激酶3β(GSK-3β)mRNA水平,Western blot法检测β联蛋白(β-catenin)、血管内皮生长因子(VEGF)、血管紧张素Ⅱ(AngⅡ)的蛋白表达。结果脑络欣通能改善模型大鼠神经功能,降低气虚血瘀证评分,恢复rCBF;脑络欣通高、中剂量组病变减轻最为明显,且这两组对Wnt5a mRNA表达的上调作用最为明显,但对模型大鼠GSK-3βmRNA无明显影响;脑络欣通高、中剂量组β-catenin、VEGF、AngⅡ表达显著升高。结论脑络欣通能促进脑血管再生而提高rCBF,可能与激活Wnt通路而影响促血管生成因子的表达有关。Objective To investigate the effect of Yiqihuoxue herb Naoluoxintong on cerebral vascular regeneration in rats of middle cerebral artery occlusion-reperfusion(MCAO-R)experimental model with Qi deficiency and blood stasis syndrome,and explore the possible mechanisms.Methods A total of 60 SD rats were randomly divided into a control group,a model group and three Naoluoxintong-treated groups[1200,800 and 400 mg/(kg·d)],with 12 rats each.Except for the control group,the other groups were treated with modified suture method combined with multi-factor compound simulation to establish the models with both MCAO-R and syndrome of Qi deficiency accompanied by blood stasis.Neural functional deficit,blood stasis syndrome and Qi deficiency syndrome were scored by quantitative criteria for biological characteristics score.The regional cerebral blood flow(rCBF)was dynamically monitored with laser Doppler scanning.HE staining was used to observe the pathological changes of brain tissue.The mRNA expression levels of Wnt5a,glycogen synthase kinase-3β(GSK-3β)were determined by real-time fluorescent quantitative PCR,and the protein expression levels ofβ-catenin,vascular endothelial growth factor(VEGF),AngⅡin the rat brain tissue were detected by Western blotting.Results Naoluoxintong improved neural functional in the model rats,reduced the scores of neural functional deficit,blood stasis syndrome and Qi deficiency syndrome,and restored rCBF simultaneously.Meanwhile,Naoluoxintong high-and middle-dose groups were better than any other model groups in terms of pathological changes,and the up-regulation of Wnt5a mRNA expression in these two groups was the most obvious.However,it had no significant effect on GSK3βmRNA in the model rats.Expression levels ofβ-catenin,VEGF,AngⅡprotein were obviously up-regulated in Naoluoxintong high-and middle-dose groups.Conclusion Naoluoxintong can improve the rCBF with the aid of promoting cerebral vascular regeneration,which might be related to high expression of pro-angiogenic factors that a

关 键 词：脑络欣通 脑缺血 WNT通路 血管再生 局部脑血流量 

分 类 号：R743.31[医药卫生—神经病学与精神病学] R322.12[医药卫生—临床医学]