摘要
目的研究对苯甲酰红景天苷(p-benzoyl salidroside,pOBz)对缺血性脑卒中后血管生成的作用及机制。方法线栓法制备MCAO模型,实验分为Sham组、MCAO组、pOBz给药组、依达拉奉阳性对照组,连续给药7 d。mNSS评估大鼠神经功能损伤;Western blot检测CD31、NICD、Hes-1蛋白表达;免疫荧光染色检测CD31阳性细胞数。构建HUVEC的OGD/R模型,经不同浓度pOBz(0.01、0.1、1μmol·L^(-1))给药后,CCK-8检测细胞存活率,体外成管实验检测血管形成能力;Western blot检测CD31、NICD、Hes-1蛋白表达,为进一步探究其作用机制,HUVEC给予DAPT作用后,分组、给药,检测上述指标变化。结果pOBz明显降低MCAO大鼠mNSS评分,增加缺血侧脑组织CD31阳性细胞数,促进MCAO大鼠CD31、NICD、Hes-1蛋白表达(P<0.01)。体外结果进一步表明pOBz能剂量依赖性提高OGD/R诱导的HUVEC存活率以及血管形成能力,促进CD31、NICD、Hes-1蛋白表达(P<0.01),且Notch抑制剂DAPT能够逆转pOBz上述作用。结论pOBz促进HUVEC血管生成,其作用机制与Notch通路有关。
Aim To study the effect of p-benzoyl salidroside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was employed to detect CD31,NICD,and Hes-1 protein expression,while immunofluorescence staining was applies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz concentrations(0.01,0.1,1μmol·L^(-1)),the CCK-8 assay was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administration,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregulated CD31,NICD,and Hes-1 protein expression(P<0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angiogenesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P<0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angiogenesis in HUVEC,and its mechanism involves activation of the Notch signaling pathway.
作者
陈景泉
江玉婷
郑雪蕊
吴慧玲
吴青青
余正双
赖文芳
洪桂祝
CHEN Jing-quan;JIANG Yu-ting;ZHENG Xue-rui;WU Hui-ling;WU Qing-qing;YU Zheng-shuang;LAI Wen-fang;HONG Gui-zhu(College of Pharmacy,Fujian University of Tranditional Chinese Medicine,Fuzhou 350122,China;Training Dept of North Fujian Health School,Nanping Fujian 354200,China)
出处
《中国药理学通报》
北大核心
2025年第12期2253-2259,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 82174001)
福建省自然科学基金资助项目(No 2024J01776)。
