Article(id=1322926680209236711, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.09.024, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793339899351, onlineDateStr=2026-10-30, pubDate=1757433600000, pubDateStr=2025-09-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339899351, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339899351, creator=13701087609, updateTime=1793339899351, updator=13701087609, issue=Issue{id=1322926492627378659, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='9', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1757433600000', pubDateStr='2025-09-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339854628, creator='13701087609', updateTime=1793340762858, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322930302095590169, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322930302095590170, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926492627378659, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=134, endPage=139, ext={EN=ArticleExt(id=1322926680423146216, articleId=1322926680209236711, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Research Progress on Mechanisms of Chinese Herbal Glycosides in Prevention and Treatment of Ischemic Stroke, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Ischemic stroke is a common and severe cerebrovascular disease primarily caused by insufficient blood supply to the brain,resulting in significant damage to brain tissue and severely impacting patients'quality of life. Despite the introduction of modern medical treatments such as recombinant tissue plasminogen activator(rt-PA)thrombolys is and mechanical thrombectomy,issues like time window limitations and bleeding risks remain challenging. In recent years,traditional Chinese medicine(TCM)hasmade remarkable progress in the treatment of ischemic stroke. TCM not only overcomes the time window limitations of traditional thrombolytic therapy but also significantly reduces bleeding risks. Among the potential treatments,Chinese herbal glycosides have been extensively used for various diseases,including ischemic stroke. This paper focused on the relationship between Chinese herbal glycosides and ischemic stroke,summarizing their mechanisms of action in antioxidation,anti-inflammation,maintenance of vascular function,neuroprotection,and regulation of gutmicrobiota. The study aimed to provide novel perspectives and approaches for the clinical treatment of ischemic stroke.

, authors=Chenming HE1, Ling LIN2, Xinxin WU3, Xiayu CUI4, Wen ZHANG1, Wei PENG1, Bangjiang FANG1, authorsList=Chenming HE, Ling LIN, Xinxin WU, Xiayu CUI, Wen ZHANG, Wei PENG, Bangjiang FANG, authorCompany=null, correspAuthors=Bangjiang FANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322926680813216489, articleId=1322926680209236711, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=中药苷类化合物防治缺血性脑卒中作用机制的研究进展, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

缺血性脑卒中是一种常见且严重的脑血管疾病,主要由于脑部供血不足而引发脑组织损害,进而严重影响患者的生活质量。尽管现代医学已经引入了诸如重组组织型纤溶酶原激活剂溶栓和机械取栓等急性治疗方法,但仍然难以回避时间窗限制和出血风险等问题。近年来,中医药在缺血性脑卒中治疗领域取得了显著进展。中医药不仅突破了传统溶栓治疗的时间窗限制,还在很大程度上降低了出血风险。其中,中药苷类化合物作为一种潜在的治疗方法,已经广泛用于多种疾病的治疗,包括缺血性脑卒中。聚焦于中药苷类化合物与缺血性脑卒中之间的关系,综合总结了它们在抗氧化、抗炎、维持血管功能、神经保护以及调节肠道菌群等多个方面的应用机制。研究旨在为临床治疗缺血性脑卒中提供全新的思路和方法。

, authors=贺晨明1, 林玲2, 邬鑫鑫3, 崔夏雨4, 张文1, 彭伟1, 方邦江1, authorsList=贺晨明, 林玲, 邬鑫鑫, 崔夏雨, 张文, 彭伟, 方邦江, authorCompany=null, correspAuthors=方邦江, authorNote=

贺晨明(1993-),男,甘肃天水人,博士研究生,研究方向:感染、脑病中西医临床与基础。

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方邦江(1965-),男,上海人,教授、主任医师,博士研究生导师,博士后,研究方向:中医药防治急危重症临床与基础。E-mail:。
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贺晨明(1993-),男,甘肃天水人,博士研究生,研究方向:感染、脑病中西医临床与基础。

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贺晨明(1993-),男,甘肃天水人,博士研究生,研究方向:感染、脑病中西医临床与基础。

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中药苷类化合物防治缺血性脑卒中作用机制的研究进展
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贺晨明 1 , 林玲 2 , 邬鑫鑫 3 , 崔夏雨 4 , 张文 1 , 彭伟 1 , 方邦江 1
中华中医药学刊 | 国家项目点击 2025,43(9): 134-139
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中华中医药学刊 |国家项目点击 2025 , 43 (9) : 134 -139
中药苷类化合物防治缺血性脑卒中作用机制的研究进展
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贺晨明(1993-),男,甘肃天水人,博士研究生,研究方向:感染、脑病中西医临床与基础。

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贺晨明1, 林玲2, 邬鑫鑫3, 崔夏雨4, 张文1, 彭伟1, 方邦江1
作者信息
  • 1.上海中医药大学附属龙华医院,上海 200032
  • 2.广州中医药大学惠州医院(惠州市中医医院),广东 惠州 516000
  • 3.同济大学附属皮肤病医院,上海 200443
  • 4.陕西中医药大学第一临床医学院,陕西 咸阳 712046
通讯作者:
方邦江(1965-),男,上海人,教授、主任医师,博士研究生导师,博士后,研究方向:中医药防治急危重症临床与基础。E-mail:。
作者简介:

贺晨明(1993-),男,甘肃天水人,博士研究生,研究方向:感染、脑病中西医临床与基础。

Research Progress on Mechanisms of Chinese Herbal Glycosides in Prevention and Treatment of Ischemic Stroke
Chenming HE1, Ling LIN2, Xinxin WU3, Xiayu CUI4, Wen ZHANG1, Wei PENG1, Bangjiang FANG1
Affiliations
  • 1.Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China
  • 2.Huizhou Hospital of Guangzhou University of Chinese Medicine(Huizhou Hospital of Traditional Chinese Medicine),Huizhou 516000,Guangdong,China
  • 3.Skin Disease Hospital of Tongji University,Shanghai 200443,China
  • 4.The First Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China
出版时间: 2025-09-10 doi: 10.13193/j.issn.1673-7717.2025.09.024
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缺血性脑卒中是一种常见且严重的脑血管疾病,主要由于脑部供血不足而引发脑组织损害,进而严重影响患者的生活质量。尽管现代医学已经引入了诸如重组组织型纤溶酶原激活剂溶栓和机械取栓等急性治疗方法,但仍然难以回避时间窗限制和出血风险等问题。近年来,中医药在缺血性脑卒中治疗领域取得了显著进展。中医药不仅突破了传统溶栓治疗的时间窗限制,还在很大程度上降低了出血风险。其中,中药苷类化合物作为一种潜在的治疗方法,已经广泛用于多种疾病的治疗,包括缺血性脑卒中。聚焦于中药苷类化合物与缺血性脑卒中之间的关系,综合总结了它们在抗氧化、抗炎、维持血管功能、神经保护以及调节肠道菌群等多个方面的应用机制。研究旨在为临床治疗缺血性脑卒中提供全新的思路和方法。

中药苷类化合物  /  缺血性脑卒中  /  作用机制  /  总结  /  综述

Ischemic stroke is a common and severe cerebrovascular disease primarily caused by insufficient blood supply to the brain,resulting in significant damage to brain tissue and severely impacting patients'quality of life. Despite the introduction of modern medical treatments such as recombinant tissue plasminogen activator(rt-PA)thrombolys is and mechanical thrombectomy,issues like time window limitations and bleeding risks remain challenging. In recent years,traditional Chinese medicine(TCM)hasmade remarkable progress in the treatment of ischemic stroke. TCM not only overcomes the time window limitations of traditional thrombolytic therapy but also significantly reduces bleeding risks. Among the potential treatments,Chinese herbal glycosides have been extensively used for various diseases,including ischemic stroke. This paper focused on the relationship between Chinese herbal glycosides and ischemic stroke,summarizing their mechanisms of action in antioxidation,anti-inflammation,maintenance of vascular function,neuroprotection,and regulation of gutmicrobiota. The study aimed to provide novel perspectives and approaches for the clinical treatment of ischemic stroke.

Chinese herbal glycosides  /  ischemic stroke  /  mechanisms of action  /  summary  /  review
贺晨明, 林玲, 邬鑫鑫, 崔夏雨, 张文, 彭伟, 方邦江. 中药苷类化合物防治缺血性脑卒中作用机制的研究进展. 中华中医药学刊, 2025 , 43 (9) : 134 -139 . DOI: 10.13193/j.issn.1673-7717.2025.09.024
Chenming HE, Ling LIN, Xinxin WU, Xiayu CUI, Wen ZHANG, Wei PENG, Bangjiang FANG. Research Progress on Mechanisms of Chinese Herbal Glycosides in Prevention and Treatment of Ischemic Stroke[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (9) : 134 -139 . DOI: 10.13193/j.issn.1673-7717.2025.09.024
缺血性脑卒中(Ischemic stroke,IS)是脑部供血不足而引发脑组织损害的神经系统疾病,具有高发病率、高致残率以及高致死率等特点[1]。全球范围内仍是第二大死亡原因,而在我国更居首位[2-3]。流行病学发现,随着人口老龄化,到2030年IS的发病率可能会增加50%左右[4]。IS的发病机制涉及能量代谢障碍、细胞凋亡、炎症反应和兴奋性氨基酸毒性作用等复杂过程[5]。血液供应不足导致神经细胞缺氧和失养,从而引发炎症反应导致细胞死亡和脑组织损伤[6]。高发病率与多种因素相关,如年龄、高血压病、高血糖、高血脂、心脏疾病等[7-8]。现代医学虽采用例如重组组织型纤溶酶原激活剂溶栓和机械取栓等急性治疗方法,但时间窗限制和出血风险等问题仍然需要考虑[9]。
中医药在IS治疗方面取得了显著突破。相较于传统的现代医学治疗方法,中医药疗法具有独特优势[10]。中医药不仅突破传统溶栓治疗的时间窗限制,还较大程度地减少出血风险[11]。中草药作为特殊的天然药物,有助于促进身体恢复与内部平衡[12]。研究表明,从中草药中提取的化合物对IS具有显著神经保护作用。这些药物可以改善大脑微循环,减轻脑缺血半黯带损伤,抑制兴奋性氨基酸引发的兴奋性毒性,并调节小胶质细胞的激活。此外,天然化合物还可通过减少氧化应激和炎症反应,保护缺血再灌注损伤[13]。近年来,随着质谱技术的发展,研究者们对中草药的化学成分进行深入研究,并从中发掘有益的化合物。其中,中药苷类药物具有抗病毒、免疫抑制、神经保护、抗癌、抗氧化、抗炎、改善微循环、兴奋性毒性抑制和细胞凋亡调节等特点,其相关信号通路逐步明晰[14-15]。苷类药物在临床实践中广泛应用,适用于多种疾病治疗,包括对IS的治疗。
苷类是糖与非糖物质的连接产物,大多数无色无臭,但黄酮苷等少数则有颜色和独特的味道。其性质涉及酸碱性、溶解性、裂解特性和光学活性。根据结构可分为氰苷、酚苷和醇苷等类别[16]。药理作用包括祛痰止咳、抗炎、免疫调节和抗肿瘤作用[17-18]。尤其在IS治疗方面应用广泛。其机制多样,太白楤木皂苷可显著改善大脑中动脉阻塞(Middle cerebral artery occlusion,MCAO)小鼠中脑梗死的面积、脑肿胀和神经功能损伤,并增加脑组织中新生血管5-溴脱氧尿嘧啶核苷(5-bromodeoxyuridinc,BrdU)和血小板-内皮细胞黏附分子(Platelet endothelial cell adhesion molecule-1,PECAM-1/CD31)双阳性表达,促进血管内皮生长因子(Vascular endothelial growth factor,VEGF)和一氧化氮(Nitric oxide,NO)的释放以及减少神经元特异性烯醇化酶(Neuron-specific enolase,NSE)和乳酸脱氢酶(Lactate dehydrogenase,LDH)的释放[19]。此外,太白楤木皂苷还可通过VEGF和NO的释放,增加VEGF、VEGFR2、磷脂酶C-γ1(Phospholipase c-gamma l,PLCγ1)、细胞外调节蛋白激酶(Extracellular regulated protein kinases,ERK1/2)、非受体酪氨酸激酶(Sarcoma receptor coactivator,Src)和内皮型一氧化氮合酶(endothelial Nitric oxide synthase,eNOS)的表达促进人脐静脉内皮细胞的存活、增殖、迁移和管状结构的形成,其机制是通过调节VEGF/VEGFR2进而调节Src/eNOS和PLCγ1/ERK1/2促进血管生成改善IS。一项随机临床试验纳入3072名IS患者,采用67家多中心、双盲、安慰剂对照的方法进行。结果发现,在服用三七皂苷的IS患者中,更有可能在3个月内达到功能独立性。在安全性方面,三七皂苷组与安慰剂组的严重不良事件发生率无显著统计学差异,表明三七总皂苷在治疗IS预后方面具有安全有效神经保护作用[20]。七叶皂苷通过降低MCAO大鼠血液中升高的皮质酮和内毒素水平,调节回肠组织中的糖皮质激素受体(Glucocorticoid receptor,GR)/p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)/核因子κB(Nuclear factor kappa-B,NF-κB)信号通路和缺血脑组织中的脂多糖(Lipopolysaccharide,LPS)/Toll样受体4(Toll-like receptor 4,TLR4)/NF-κB信号通路来减轻缺血性脑损伤[21]。此外,联合应用芍药苷和毛蕊异黄酮苷可显著改善大脑中动脉栓塞/再灌注(Middle cerebral artery occlusion/reperfusion,MCAO/R)大鼠的神经功能,并降低脑损伤。其作用机制涉及调节磷酸肌醇3-激酶(Phosphatidylinositide 3-kinase,PI3K)/蛋白激酶B(Protein kinase B,AKT)和B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)/兔抗人单克隆抗体(Bcl-2-Associated X,BAX)信号通路,并在细胞实验中抑制细胞凋亡和活性氧(Reactive oxygen species,ROS)生成。这种协同保护作用可能成为IS治疗的新策略,并具备重要的临床应用前景[22]。因此,中药中的苷类化合物通过多种途径来发挥对IS的调控作用,包括抗氧化、抗炎、维持血管功能、神经保护、调节肠道菌群等。
IS的病理机制中,氧化应激起到十分重要的作用。由于脑血管阻塞引起脑部缺氧,会产生大量ROS物质,例如超氧阴离子和过氧化氢,进而引发氧化应激[23]。这些活性氧物质与细胞成分相互作用,导致蛋白质氧化、脂质过氧化等反应,加剧脑组织的氧化损伤[24]。Han等研究发现,红景天苷能够显著提高超氧化物歧化酶和谷胱甘肽-S-转移酶的活性,降低马来醛水平。此外,红景天苷还通过增加核因子NF-E2相关因子(Nuclear factor-erythroid 2-related factor 2,Nrf2)和血红素氧合酶-1的表达,发挥其抗氧化作用[25]。陈兴等研究通过MCAO小鼠发现,连翘酯苷B能够降低氧化应激标记物,提高抗氧化酶活性,并增加单磷酸腺苷激活的蛋白激酶[Adenosine 5‘-monophosphate(AMP)-activated protein kinase,AMPK]、基因编码的人类蛋白质(Forkhead box O3,FOXO3)磷酸化和寿命调控因子(Abnormal dauer formation protein-16,DAF-16)的表达水平。进一步的AMPK抑制实验证明,连翘酯苷B可通过促进AMPK磷酸化和DAF-16蛋白的表达以及FOXO3磷酸化,增加抗氧化酶表达,清除ROS[26]。贵州民族药木姜叶柯的活性成分三叶苷能够激活沉默信息调节因子3(Silent information regulator of transcription 3,SIRT3)、TLR4/NF-κB和Nrf2/Kelch样ECH相关蛋白1(Kelch-like ECH-associated protein 1,Keap1)信号途径,同时减轻氧化应激并抑制载脂蛋白E4(Apolipoprotein E4,APOE4)/环孢菌素A结合蛋白(Cyclophilin A,CypA)/基质金属蛋白酶9(Matrix Metalloproteinase 9,MMP9)信号途径减少血脑屏障损伤[27]。红花中的单查尔酮苷类化合物羟基红花黄素A通过抑制线粒体膜通透性转换孔(mitochondrial Permeability transition pore,mPTP),改善神经功能损伤、降低氧化应激和TNF-α炎症表达,减少梗死体积[28]。综上,红景天苷、连翘酯苷B以及三叶苷等药物在不同研究中显示出抗氧化作用。其机制包括抑制氧化应激、调节抗氧化酶活性以及激活Nrf2、SIRT3等信号途径,从而减轻炎症反应、清除ROS,保护神经组织免受缺血再灌注损伤。这些研究为开发治疗IS的新策略提供了有益的策略。
除氧化应激外,炎症反应在IS也起着重要角色[29]。IS导致炎症反应的释放,如肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-1β(Interleukin-1 beta,IL-1β)和白细胞介素-6(Interleukin-6,IL-6),并激活免疫细胞和炎症反应,加剧了脑损伤[30]。炎症反应的破坏会破坏血脑屏障,促进细胞死亡,因此研究抑制炎症的策略对于脑卒中治疗至关重要。研究发现,淫羊藿苷能够降低炎症细胞因子IL-1β的表达,抑制炎症反应从而减轻缺血再灌注损伤所导致的神经功能缺陷、脑水肿和病理损伤[31]。此外,淫羊藿苷还可以通过抑制内质网应激通路,降低相关蛋白的表达发挥神经保护作用。另一项研究指出,淫羊藿苷通过抑制NFκB、过氧化物酶体增殖物激活受体α(Perixisome proliferator-activated receptor alpha,PPARα)和PPARγ介导的炎症反应减轻脑损伤[32]。三七总皂苷可以通过下调TLR4/NF-κB信号通路的方式,降低IL-1β和TNF-α水平,提高IL-4和IL-10水平,从而保护脑缺血再灌注损伤[33]。此外,三七皂苷还可以抑制TNF-α、IL-1β和细胞间黏附分子-1(Intercellular cell adhesion molecule-1,ICAM-1)的表达[34]。研究发现,西红花苷通过降低IL-1炎症因子的表达,改善卒中后抑郁大鼠的抑郁状态[35]。Hao等研究发现,黄芩苷可通过抑制脑缺血再灌注损伤中TLR2/TLR4受体及下游信号的方式,减少环氧化酶2(Cyclooxygenase,COX2)、TNF、IL6、IL-1β、诱导型一氧化氮合酶(inducible Nitric Oxide Synthase,iNOS)等促炎因子的表达[36]。因此,通过分析发现淫羊藿苷、三七总皂苷、西红花苷、黄芩苷等药物能有效抑制IS的炎症反应,减轻促炎因子的表达,增加抑炎因子的水平,并通过不同机制干预炎症应答,从而减轻脑损伤。
维持血管功能对于治疗IS的严重损伤至关重要。脑缺血会导致氧化应激、炎症和细胞死亡,进而损害血管内皮细胞和血脑屏障(Blood brain barrier,BBB)[37]。保护血脑屏障的完整性、维持血管内皮细胞的正常功能以及促进血管修复有助于减轻脑损伤[38]。研究发现仙茅苷A可通过血管细胞黏附分子-1(Vascular cell adhesion molecule-1,VCAM-1)/早期生长反应3(Early growth response 3,EGR3)/cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)/VEGF和Wnt家族成员5A(Wnt family member 5A,Wnt5A)/β-连环蛋白(β-catenin)多条信号通路促进血管新生,增强人脑微血管内皮细胞和平滑肌细胞的增殖,加速毛细血管样结构的形成[39]。此外,仙茅苷A还可以改善脑缺血损伤后大鼠的血脑屏障和神经功能[40]。Chen研究发现,三七皂苷能够通过PI3K/AKT/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路提高VEGF的表达,促进内皮细胞的增殖和迁移,推动血管新生[41]。此外,它还增加血管生成关键因子VEGFR2的表达,引导新的血管支路的生成,在血管三维空间的扩展方面起到了积极的作用[42]。通过血清药理学实验,研究发现含有10%毛蕊异黄酮苷的药血清可显著促进内皮祖细胞(Endothelial progenitor cells,EPCs)的迁移和管腔形成能力。含药血清中的VEGF、基质细胞衍生因子-1(Stromal cellderived factor-1,SDF-1)、粒细胞集落刺激因子(Granulocyte colony stimulating factor,G-CSF)、粒细胞-巨噬细胞集落刺激因子(Granulocyte-macrophage colony stimulating factor,GM-CSF)和促红细胞生成素(Erythropoietin,EPO)的含量也显著增加,这些物质在激活EPCs并参与脑缺血后血管再生修复中具有关键作用[43]。研究还发现,红景天苷能够降低血脑屏障的通透性,减少脑缺血组织的含水量[44]。该化合物能够抑制基质金属蛋白酶的激活,恢复紧密连接蛋白,从而改善受损的血脑屏障[45-46]。此外,红景天苷还可通过抑制炎症和凋亡,提高内皮一氧化氮合酶的表达,并减轻氧化应激引起的内皮细胞损伤,进一步维持血管内稳态[47-48]。网络药理学发现,黄芪甲苷具有改善脑血流、减轻神经功能损伤对IS治疗效果的作用,其作用机制涉及多个靶点如AKT丝氨酸/苏氨酸激酶1(AKT serine/threonine kinase 1,AKT1)、肾素(Renin gene,REN)、表皮生长因子受体(Epidermal growth factor receptor,EGFR)、VEGFA和非受体酪氨酸激酶(non-receptor tyrosine kinase Gene,SRC)等,可以促进血管生成并抑制血小板活性[49]。Shi等的研究发现,金丝桃苷可通过三磷酸肌醇(Inositol triphosphate,IP3)/蛋白激酶C(Protein Kinase C,PKC)信号通路激活瞬时感受器电位香草酸受体4(Transient Receptor Potential Vanilloid 4,TRPV4)通道来修复脑损伤,从而促进血管内皮细胞的依赖性超极化并打开SKca和IKca通道[50]。另外,栀子苷能通过降低B型内皮素受体(Endothelin receptor type B,EDNRB)的表达,起到保护缺血性损伤脑微血管内皮细胞的作用[51]。综合来看,中药苷类化合物在维持血管功能和治疗IS方面具有重要潜力。这些化合物能够通过促进血管新生、调节血管内皮细胞功能、减轻血脑屏障损伤、抑制炎症反应和氧化应激等多种途径来保护神经血管单元,减轻脑损伤,并在IS治疗中起到积极作用。
神经保护的目标是最大限度地减少脑组织损伤,保护神经细胞的存活和功能[52]。许多中药表现出神经保护作用,通过多种途径如促进细胞存活等发挥作用[53]。孙玥光等研究发现黄芩苷能显著改善MCAO大鼠的神经功能,减轻脑梗死,并抑制IL-33/ST2L通路与IL-6、TNF-α水平,降低小胶质细胞数目[54]。周密等研究发现鸢尾甲苷B能显著减轻PC12细胞在氧糖剥夺体外脑卒中模型中的细胞损伤,提高存活率,降低细胞内钙离子、乳酸脱氢酶和活性氧水平,并减少细胞凋亡,从而发挥神经保护作用[55]。严啸东等研究发现,菸花苷显著提高MCAO大鼠的生存率,促进体质量增加,减轻脑组织病理损伤,保护脑神经元形态和神经系统功能,并实现对IS神经保护效应的机制[56]。基于生物信息学研究发现红景天苷可以通过TAL1/Nr4a1/mir-19a-3p轴发挥对缺血/再灌注的脑保护作用[57]。黄芪中的黄芪甲苷可以通过下调IL-1β含量、抑制基质金属肽酶9(Matrix metallopeptidase 9,MMP-9)蛋白的表达发挥对脑缺血再灌注后血脑屏障的保护作用及其机制[58]。王国峰等研究发现,芍药中的芍药苷可以降低大鼠脑中动脉梗死模型的梗死体积,改善神经功能,并通过抑制COX2、5-脂氧合酶(5-lipoxygenase,5-LOX)的表达以及活化MAPK通路来发挥神经保护作用[59]。邓凤春等研究发现,刺五加苷B通过激活PI3K/AKT信号通路来减轻缺氧/复氧诱导的神经元凋亡,显著提高大鼠皮层神经元的活力,降低与细胞凋亡密切相关的蛋白水解酶蛋白的表达[60]。獐牙菜苦苷通过抑制TLR4/NF-κB/PARP1信号通路来减轻细胞内炎症反应干预糖氧剥夺再灌注过程,降低细胞中TLR-4、MyD88、NF-κB p65和DNA修复酶1(poly ADP-ribose polymerase 1,PARP1)的表达水平,对受损脑组织起到保护作用[61]。此外,黄芩苷与栀子苷的联合应用可以降低脑卒中大鼠半胱氨酰白三烯的水平,减轻脑缺血引起的神经功能损害。同时,它还可以通过抑制5-LOX、半胱氨酰白三烯受体1和半胱氨酰白三烯受体2的表达来发挥神经保护作用[62]。综合多项研究表明,中药在神经保护领域具有广泛的应用潜力。黄芪苷、鸢尾甲苷B、菸花苷、红景天苷以及芍药甘草汤中的芍药苷、刺五加苷B和獐牙菜苦苷等中药成分,在IS等神经疾病中发挥显著的神经保护作用。这些研究为揭示中药的神经保护机制以及开发创新的神经保护药物提供了有益的线索。
IS会导致肠道屏障功能受损,破坏肠道上皮细胞完整性,增加肠道通透性,从而引起菌群移位和失衡[63]。IS还会释放大量炎性物质,对肠道组织造成损伤,破坏紧密连接结构,影响肠道屏障功能[64]。因此,调节肠道菌群失衡、修复屏障受损以及减轻炎症反应成为IS治疗的新途径[65]。三七皂苷与肠道菌群和IS之间存在相互作用。三七皂苷可以抑制脑缺血/再灌注损伤引发的肠道菌群减少,并增强SD大鼠海马区γ氨基丁酸的表达,从而产生神经保护效应。然而,在无菌鼠中,这种作用则可减弱[66]。研究使用16S测序技术发现,黄芪皂苷Ⅳ能够逆转急性IS引发的肠道微生物双歧杆菌属、大肠杆菌属、布劳提氏菌属、霍德曼内拉菌属和梭菌属的丰度增加,同时减少同型半胱氨酸和甘油三酯的含量。动物实验中,急性IS粪便样本引发了自噬活性的增强、氧化应激和炎症反应,黄芪皂苷Ⅳ的处理能够逆转这些变化,并且不影响运动功能。表明黄芪皂苷Ⅳ具有治疗急性IS的潜力[67]。红景天苷与多索吗啡联合治疗能有效改善MCAO大鼠神经功能损伤,减少脑梗死面积。肠道菌群分析表明,这种联合作用可以丰富有益菌,重塑肠道微生态,改善微生物失调[68]。另外,联合应用还能通过调节肠-脑屏障相关蛋白的表达,减弱肠道菌群的移位,降低全身炎症反应,从而保护脑缺血再灌注损伤。这些研究聚焦于IS对肠道菌群及神经保护的影响以及药物干预策略。三七皂苷和红景天苷联合多索吗啡治疗可改善脑损伤,恢复神经功能,同时调整肠道微生态,维护肠-脑屏障。黄芪皂苷Ⅳ逆转脑卒中引发的菌群紊乱和炎症,具有治疗潜力。这些发现强调肠道与脑的密切联系,为IS治疗提供新视角。
中药苷类化合物在IS治疗中呈现出广阔的前景。通过多种作用机制,包括抗氧化、抗炎、维持血管功能、神经保护和调节肠道菌群等途径,这些化合物展现出显著的神经保护潜力。然而,笔者认为,尽管取得了诸多的成果,但仍面临一些亟待解决的问题和挑战。首先,在细胞和动物模型中取得了显著效果,但中药苷类化合物的临床转化尚需更多研究。临床试验设计、样本数量、治疗方案等需要精心考虑,确保治疗安全性和有效性得到准确评估。其次,中药复杂的成分和多样的作用机制增加了研究的复杂性。深入探究中药苷类化合物的作用机制需要考虑不同成分的相互作用、剂量效应和药物代谢途径,以更好理解其在IS中的作用方式。此外,药物剂量和用法的优化也是关键问题。不同的中药苷类化合物可能对剂量和用法有不同要求,需要更多研究确定最佳治疗方案,以确保临床应用的安全性和有效性。另外,虽然中药苷类化合物在神经保护中表现出多重作用,但其具体的作用机制和相互关系仍需进一步阐明。深入的分子生物学和细胞生物学研究可揭示这些化合物如何影响不同信号通路和分子途径,更好指导临床应用。
  • 国家自然科学基金项目(81973811)
  • 国家中医药管理局高水平中医药重点学科建设项目-中医急诊学(20230504)
  • 国家中医药管理局中医药传承与创新“百千万”人才工程(岐黄工程)“岐黄学者”项目(国中医药人教发〔2018〕12号)
  • 广州中医药大学惠州医院科研课题创新基金项目(2023CXJJ006)
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2025年第43卷第9期
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doi: 10.13193/j.issn.1673-7717.2025.09.024
  • 首发时间:2026-10-30
  • 出版时间:2025-09-10
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国家自然科学基金项目(81973811)
国家中医药管理局高水平中医药重点学科建设项目-中医急诊学(20230504)
国家中医药管理局中医药传承与创新“百千万”人才工程(岐黄工程)“岐黄学者”项目(国中医药人教发〔2018〕12号)
广州中医药大学惠州医院科研课题创新基金项目(2023CXJJ006)
作者信息
    1.上海中医药大学附属龙华医院,上海 200032
    2.广州中医药大学惠州医院(惠州市中医医院),广东 惠州 516000
    3.同济大学附属皮肤病医院,上海 200443
    4.陕西中医药大学第一临床医学院,陕西 咸阳 712046

通讯作者:

方邦江(1965-),男,上海人,教授、主任医师,博士研究生导师,博士后,研究方向:中医药防治急危重症临床与基础。E-mail:。
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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