[1]熊英琼,江铃铃,彭毓棻,等.基于磷脂酰肌醇3激酶/蛋白激酶B信号通路探究麦冬皂苷D对脑缺血再灌注损伤的神经保护作用[J].陕西医学杂志,2026,(1):35-42.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.006]
 XIONG Yingqiong,JIANG Lingling,PENG Yufen,et al.Exploring the neuroprotective effect of ophiopogonin D on cerebral ischemia-reperfusion injury based on the PI3K/AKT signaling pathway[J].,2026,(1):35-42.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.006]
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基于磷脂酰肌醇3激酶/蛋白激酶B信号通路探究麦冬皂苷D对脑缺血再灌注损伤的神经保护作用

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年1期
页码:
35-42
栏目:
基础研究
出版日期:
2026-01-05

文章信息/Info

Title:
Exploring the neuroprotective effect of ophiopogonin D on cerebral ischemia-reperfusion injury based on the PI3K/AKT signaling pathway
作者:
熊英琼1江铃铃2彭毓棻1 黄招君1李小兵1 万琛宜1
( 1.南昌大学第一附属医院神经内科,江西 南昌 330006;2.江西中医药大学研究生院,江西 南昌330006)
Author(s):
XIONG Yingqiong1JIANG Lingling2PENG Yufen1HUANG Zhaojun1LI Xiaobing1WAN Chenyi1
(1.Department of Neurology,First Affiliated Hospital of Nanchang University,Nanchang 330006,China;2.Graduate School of Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China)
关键词:
缺血性脑卒中脑缺血再灌注麦冬皂苷D神经保护炎症凋亡
Keywords:
ischemic strokeCerebral ischemia-reperfusionOphiopogonin DNeuroprotectionInflammationApoptosis
分类号:
R 743
DOI:
DOI:10.3969/j.issn.1000-7377.2026.01.006
文献标志码:
A
摘要:
目的:探讨麦冬皂苷D(OPD)单用或与依达拉奉(Edaravone)联用通过调控磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路对脑缺血再灌注损伤(CIRI)的神经保护作用。方法:120只雌性C57BL/6小鼠,随机分为Sham组、脑缺血再灌注(MCAO/R)组、OPD组、Edaravone组和OPD+Edaravone组,每组24只。制备小鼠右侧大脑MCAO/R模型,脑缺血1 h后按分组方案给药,1次/d,持续7 d。每日称量体重,对小鼠进行神经行为学评分;转棒实验和旷场实验评估小鼠运动功能;激光散斑实验观察脑血流恢复情况;TTC染色观察脑梗死体积;HE染色、尼氏染色观察炎性细胞浸润以及神经元情况;WB检测缺血半暗带区相关蛋白表达。结果:造模后第5天和第7天,OPD、Edaravone及OPD+Edaravone组小鼠体重显著高于MCAO/R组(均P<0.01)。Zea-Longa神经评分显示,与MCAO/R组比较,三个治疗组第5天和第7天神经功能损伤明显减轻(均P<0.05)。与MCAO/R组比较,三个治疗组第3天和第7天停留时间显著延长,运动距离显著增加(均P<0.05)。OPD、Edaravone及OPD+Edaravone组小鼠在再灌注3 d和7 d的局部脑血流量(rCBF)比值显著增加(均P<0.05),脑梗死体积明显减少(P<0.001)。HE和Nissl染色显示,三个治疗组脑组织损伤减轻,炎性细胞浸润减少,细胞凋亡改善,尼氏小体减少减轻。WB结果表明,与MCAO/R组比较,三个治疗组Arg1、Bcl-xL、p-PI3K/PI3K和p-AKT/AKT蛋白表达显著升高,Iba1和iNOS蛋白表达显著下降(均P<0.05),同时OPD+Edaravone组Iba1和iNOS蛋白表达比较单独OPD组或单独Edaravone组显著降低(均P<0.05)。结论:麦冬皂苷D单用或与依达拉奉联用可显著缓解脑缺血再灌注损伤后的体重减轻、神经功能缺损、运动功能障碍,并通过激活PI3K/AKT信号通路改善炎症反应和抑制神经元凋亡。
Abstract:
Objective:To explore the neuroprotective effect of ophiopogonin D (OPD) alone or in combination with Edaravone on cerebral ischemia-reperfusion injury (CIRI) by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.Methods:A total of 120 female C57BL/6 mice were randomly assigned to five groups (n=24 per group):Sham group,cerebral ischemia-reperfusion (MCAO/R) group,OPD group,edaravone group,and OPD+edaravone group.Middle cerebral artery occlusion-reperfusion (MCAO/R) models were established in mice,followed by daily drug administration according to group assignments after 1 hour of cerebral ischemia,lasting for 7 days.Body weight and neurological behavior scores were recorded daily.Motor function was evaluated using rotarod and open field tests,cerebral blood flow recovery was monitored by laser speckle imaging,cerebral infarct volume was measured by TTC staining,and inflammatory cell infiltration and neuronal morphology were assessed via HE and Nissl staining.Western blotting was used to examine protein expression in the ischemic penumbra regions.Results:On day 5 and day 7 post-modeling,body weight was significantly higher in OPD,edaravone,and OPD+edaravone groups compared to the MCAO/R group (all P<0.01).Zea-Longa neurological scores showed that neurological deficits were significantly alleviated on day 5 and day 7 in all three treatment groups compared to the MCAO/R group (all P<0.05).The three treatment groups exhibited prolonged retention time and increased locomotion distance on day 3 and day 7 (all P<0.05).Regional cerebral blood flow (rCBF) ratios were significantly increased in OPD,edaravone,and OPD+edaravone groups at 3 and 7 days post-reperfusion (all P<0.05),accompanied by markedly reduced cerebral infarct volumes (P<0.001).HE and Nissl staining revealed attenuated brain tissue damage,reduced inflammatory cell infiltration,improved neuronal apoptosis,and preserved Nissl bodies in all treatment groups.Western blotting demonstrated that compared to the MCAO/R group,treatment groups showed upregulated Arg1 and Bcl-xL expression,increased ratios of p-PI3K/PI3K and p-AKT/AKT,and downregulated Iba1 and iNOS expression (all P<0.05).Notably,Iba1 and iNOS expression levels in the OPD+edaravone group were significantly lower than those in either the OPD or edaravone monotherapy groups (all P<0.05).Conclusion:Ophiopogonin D alone or combined with edaravone effectively alleviates weight loss,neurological deficits,and motor dysfunction following cerebral ischemia-reperfusion injury,exerting anti-inflammatory and anti-apoptotic effects through activation of the PI3K/AKT signaling pathway.

参考文献/References:

[1]中国心血管健康与疾病报告2024概要[J].中国循环杂志,2025,40(6):521-559.
[2]施嘉华,陈真珍,黄龙坚,等.铁死亡在脑缺血再灌注中的作用研究进展[J].陕西医学杂志,2024,53(1):132-135.
[3]何俊芳,刘新平,吕学海,等.PI3K/AKT信号通路介导脂联素对脑缺血再灌注大鼠的保护作用[J].中国卒中杂志,2022,17(8):857-862.
[4]GONG Y H,QIU J X,JIANG T,et al.Maltol ameliorates intervertebral disc degeneration through inhibiting PI3K/AKT/NF-κB pathway and regulating NLRP3 inflammasome-mediated pyroptosis[J].Inflammopharmacology,2022,31(1):369-384.
[5]高京,刘飞祥,张运克.中药调控PI3K/Akt信号通路治疗脑缺血再灌注损伤的研究进展[J].中国实验方剂学杂志,2024,30(6):253-261.
[6]迟宇昊,李暘,申远.麦冬化学成分及药理作用研究进展[J].新乡医学院学报,2021,38(2):189-192.
[7]CHEN Q K,WANG Z S,LEI B H,et al.Ophiopogonin D:Review of pharmacological activity[J].Frontiers in Pharmacology,2024,15:1401627.
[8]WANG L,YANG H B,QIAO L,et al.Ophiopogonin D inhibiting epithelial NF-κB signaling pathway protects against experimental colitis in mice[J].Inflammation,2022,45(4):1720-1731.
[9]HUANG X,JI Q,SHE C Y,et al.Ophiopogonin D ameliorates non-alcoholic fatty liver disease in high-fat diet-induced obese mice by improving lipid metabolism,oxidative stress and inflammatory response[J].Experimental and therapeutic medicine,2023,26(3):418.
[10]XU L L,GAO Y R,HU M,et al.Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO-1 signaling pathway in mice[J].Fundamental & Clinical Pharmacology,2022,36(5):790-800.
[11]EI Y,XU L,LIU R,et al.Ophiopogonin D mitigates doxorubicin-induced cardiomyocyte ferroptosis through the β-catenin/GPX4 pathway[J].Frontiers in Pharmacology,2025,16:1586937.
[12]BAO S C,CHEN T,ZHANG J X,et al.Multi-omics analysis reveals the mechanism of action of ophiopogonin D against pulmonary fibrosis[J].Phytomedicine,2023,121:155078.
[13]马汉宁,姬艳燕,陈伟,等.甘草次酸通过抑制Caspase 3/Bax/Bcl-2凋亡信号通路保护心脏骤停心肺复苏大鼠心脏功能[J].中药药理与临床,2019,35(4):28-33.
[14]ZHENG W,LI T F,WEI J P,et al.Edaravone alleviates lung damage in mice with hypoxic pulmonary hypertension by increasing nitric oxide synthase 3 expression[J].The Korean Journal of Physiology & Pharmacology:Official Journal of The Korean Physiological Society And The Korean Society of Pharmacology,2023,27(3):209-220.
[15]PAN D,RAO X,GONG M,et al.Polygonatum cyrtonema hua polysaccharides regulates NF-κB and Nrf2 pathways to alleviates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury[J].Signa Vitae:Journal For Intesive Care And Emergency Medicine,2024,20(12):108-115.
[16]张艾嘉,王爽,王萍,等.缺血性脑卒中的病理机制研究进展及中医药防治[J].中国实验方剂学杂志,2020,26(5):227-240.
[17]KURIAKOSE D,XIAO Z C.Pathophysiology and treatment of stroke:Present status and future perspectives[J].Int J Mol Sci,2020,21(20):7609.
[18]易倩,张合富,李官翔,等.麦冬多糖对破骨细胞分化的影响研究[J].现代医药卫生,2024,40(2):190-195.
[19]赵玲琳,张勇,薛慧,等.麦冬皂苷D对大鼠心肌细胞缺氧复氧损伤的保护作用及机制研究[J].中国循环杂志,2022,37(2):178-184.
[20]张光晨,王一豪,阮盼盼,等.麦冬皂苷D对异丙肾上腺素诱导的心肌细胞损伤的保护作用及靶点初探[J].中国中药杂志,2022,47(10):2721-2728.
[21]LI T,ZHAO J,GAO H.Depletion of arg1-positive microglia/macrophages exacerbates cerebral ischemic damage by facilitating the inflammatory response[J].Int J Mol Sci,2022,23(21):13055.
[22]付春丽,王俊海.急性缺血性脑卒中病人血清ARG1、ITGAM表达水平与病情及预后的关系[J].中西医结合心脑血管病杂志,2022,20(7):1319-1322.
[23]黄钰婷,周升,黄佳丽,等.小胶质细胞活化对脑缺血再灌注大鼠缺血区域神经元树突棘的影响[J].中国老年学杂志,2024,44(20):5005-5009.
[24]ZAHRA M,ZAHRA R,MARYAM A,et al.Neuroprotective effect of wild lowbush blueberry (Vaccinium angustifolium) on global cerebral ischemia/reperfusion injury in rats:Downregulation of iNOS/TNF-α and upregulation of miR-146a/miR-21 expression[J].Phytotherapy Research:PTR,2021,35(11):6428-6440.

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备注/Memo

备注/Memo:
江西省中医药管理局科技计划项目(2022A309)
更新日期/Last Update: 2026-01-05