从调控血管内皮生长因子及其受体激活Notch信号通路角度探讨生地梓醇促血管新生及神经功能重塑作用  

Effect of Shengdi Catalpol in Promoting Angiogenesis and Neural Function Remodeling by Regulating Vascular Endothelial Growth Factor and Its Receptors to Activate Notch Signaling Pathway

作　　者：孙立平 周霞[2] 刘炬 张佳乐 王祥煜 郭炳杉 刘伟 SUN Liping;ZHOU Xia;LIU Ju;ZHANG Jiale;WANG Xiangyu;GUO Bingshan;LIU Wei(Department of the First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Jinan 250001,China;Department of Rehabilitation Medicine,the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250001,China;Medical Research Center,the First Affiliated Hospital of Shandong First Medical University,Jinan 250001,China)

机构地区：[1]山东中医药大学第一临床医学院,山东省济南市250001 [2]山东中医药大学第二附属医院康复医学科,山东省济南市250001 [3]山东第一医科大学第一附属医院医学研究中心,山东省济南市250001

出　　处：《实用心脑肺血管病杂志》2021年第11期63-68,共6页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：山东省自然科学基金资助项目(ZR2019MH128)——基于VEGF-Notch-Ang信号通路探讨生地梓醇的促血管新生与神经重塑效应。

摘　　要：背景近几年较多研究发现了生地梓醇的脑保护作用,但其具体机制尚未完全明确。以血管内皮生长因子(VEGF)及其受体为切入点,研究生地梓醇的促血管新生及神经功能重塑作用,对于其在临床中的应用具有重要意义。目的从调控VEGF及血管内皮生长因子受体(VEGFR)激活Notch信号通路角度探讨生地梓醇促血管新生及神经功能重塑作用。方法本研究时间为2019年7月至2021年1月。将24只SPF级雄性SD大鼠随机分为生地梓醇组、生理盐水组、假手术组,各8只。生地梓醇组、生理盐水组大鼠参照Longa改良线栓法进行脑卒中造模,大鼠清醒后2 h采用Longa 5分法进行神经功能评分,评分1~3分视为造模成功。剔除神经功能评分为0、4分或在手术过程中死亡的大鼠,然后重新选取大鼠进行造模,补充到相应组别中,保证每组动物数量始终为8只。脑卒中造模成功后24 h,生地梓醇组大鼠腹腔注射生地梓醇溶液(9 mg/kg),生理盐水组和假手术组大鼠均腹腔注射等量的0.9%氯化钠溶液,1次/d,连续7 d。分别于造模后1、5、8 d评估各组大鼠神经功能评分、平衡木实验评分,观察各组大鼠病灶区脑组织形态,检测脑组织VEGF、VEGFR、Notch1、Notch4 mRNA相对表达量。结果干预方法与时间在神经功能评分、平衡木实验评分上存在交互作用(P<0.05);干预方法、时间在神经功能评分、平衡木实验评分上主效应显著(P<0.05)。生理盐水组、生地梓醇组大鼠造模后1、5、8 d神经功能评分、平衡木实验评分高于假手术组(P<0.05);生地梓醇组大鼠造模后5、8 d神经功能评分、平衡木实验评分低于生理盐水组(P<0.05)。生理盐水组、生地梓醇组大鼠造模后5、8 d神经功能评分、平衡木实验评分分别低于本组造模后1 d(P<0.05);生理盐水组、生地梓醇组大鼠造模后8 d神经功能评分、平衡木实验评分分别低于本组造模后5 d(P<0.05)。假手术组大Background In recent years, many studies have discovered the protective effect of Shengdi catalpol, but its specific mechanism has not yet been fully clarified. Taking vascular endothelial growth factor(VEGF) and its receptors as the entry point, the angiogenesis and nerve function remodeling effects of Shengdi catalpol are of great significance for its clinical application. Objective To explore the effect of Shengdi catalpol in promoting angiogenesis and neural function remodeling from the perspective of regulating VEGF and vascular endothelial growth factor receptor(VEGFR) to activate the Notch signaling pathway. Methods This study was conducted from July 2019 to January 2021. Twenty-four SPF male SD rats were randomly divided into Shengdi catalpol group, normal saline group and sham operation group, with 8 rats in each group. The rats in catalpol group and normal saline group were modeled according to the Longa modified suture method, neural function score was measured by Longa 5-point method at 2 h after the rats awake, and the neural function score of 1 to 3 indicated that the modeling was successful. The rats with neural function score of 0 or 4 or which died during the operation were excluded, and then the rats were re-selected for modeling and added to the corresponding groups to ensure that the number of animals in each group was always 8.Twenty-four hours after the successful modeling of stroke, the rats in the Shengdi catalpol group were intraperitoneally injected with Shengdi catalpol solution(9 mg/kg), the rats in the normal saline group and the sham operation group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution, once a day for 7 consecutive days. The neural function score and balance beam test score of rats in each group were evaluated at 1, 5 and 8 days after modeling, the brain tissue morphology of rats in each group was observed, and the relative expressions of VEGF, VEGFR, Notch1 and Notch4 mRNA were detected.Results There was an interaction between interve

关 键 词：卒中 大鼠 生地梓醇 血管新生 神经功能重塑 血管内皮生长因子 NOTCH信号通路 

分 类 号：R743[医药卫生—神经病学与精神病学]