黄芩苷pH敏感纳米粒抗乳腺癌生长作用研究

-PAGE6摘要本文首先对黄芩苷（Baicalin，BA）进行处方前研究，确定其物理化学性质。其次采用其次利用受控去溶剂化（凝聚）法制备载黄芩苷的pH响应叶酸白蛋白纳米粒，后建立黄芩苷的含量测定方法，并通过专属性实验、精密度实验、回收率测定，验证该含量测定方法的合理性。后通过改变BSA-FA@mPEG溶液浓度、反应pH以及搅拌转速，确定制备纳米粒的最优处方和工艺。最后通过红外光谱法验证BA是否被成功包裹在纳米粒内，并通过测定mPEG链解离率验证所制备纳米粒是否具有pH敏感性，最后对最优处方和工艺所制备的纳米粒进行载药量和包封率验证，评价该方法的重现性。关键词：纳米、乳腺癌、叶酸、pH敏感、黄芩苷

ABSTRACTThisarticlefirstconductspre-formulationstudiesonbaicalin(BA)todetermineitsphysicochemicalproperties.Next,itutilizesthecontrolleddesolvation(coacervation)methodtopreparepH-responsivefolatealbuminnanoparticlesloadedwithbaicalin.Then,acontentdeterminationmethodforbaicalinisestablished,andtherationalityofthiscontentdeterminationmethodisverifiedthroughspecificityexperiments,precisionexperiments,andrecoveryratedetermination.Subsequently,bychangingtheconcentrationofBSA-FA@mPEGsolution,reactionpH,andstirringspeed,theoptimalformulationandprocessforpreparingnanoparticlesaredetermined.Finally,infraredspectroscopyisusedtoverifywhetherBAhasbeensuccessfullyencapsulatedinthenanoparticles,andthepHsensitivityofthepreparednanoparticlesisverifiedbymeasuringthedissociationrateofthemPEGchain.Finally,thedrugloadingandencapsulationefficiencyofthenanoparticlespreparedbytheoptimalformulationandprocessareverified,andthereproducibilityofthismethodisevaluated.Keywords：Nanometer,Breastcancer,Folicacid,pH-sensitive,Baicalin目录摘要 IIIABSTRACT IV1前言 11.1乳腺癌与肿瘤酸性微环境 11.2黄芩苷 11.3纳米药物递送系统 31.3.1白蛋白纳米制剂 31.3.2pH敏感纳米制剂 31.3.3主动靶向纳米制剂 41.4研究内容与意义 42材料和方法 52.1仪器和材料 52.2黄芩苷处方前探究 52.3载黄芩苷pH响应叶酸白蛋白纳米粒处方工艺 62.3.1叶酸白蛋白纳米载体制备 62.3.2pH响应聚合物材料的制备 62.3.3pH响应偶联叶酸白蛋白纳米载体的制备 72.3.4载黄芩苷pH响应叶酸白蛋白纳米粒的制备 82.4含量测定方法的确定 92.4.1测定波长 92.4.2专属性实验 92.4.3标准曲线绘制 92.4.4精密度实验 102.4.5回收率测定 102.5处方工艺优化 102.5.1BSA-FA@mPEG溶液浓度考察 102.5.2反应pH考察 102.5.3搅拌转速考察 102.6载黄芩苷pH响应叶酸白蛋白纳米粒的理化性质 112.6.1红外光谱验证 112.6.2pH敏感性考察 112.6.3载药量和包封率测定 113结果 133.1含量测定方法的确定 133.1.1专属性实验 133.1.2标准曲线绘制 143.1.3精密度实验 143.1.4回收率测定 153.2处方工艺优化 152.5.1BSA-FA@mPEG溶液浓度考察 152.5.2反应pH考察 152.5.3搅拌转速考察 163.3载黄芩苷pH响应叶酸白蛋白纳米粒的理化性质 163.6.1红外光谱验证 163.6.2pH敏感性考察 173.6.3载药量和包封率测定 18结论 19参考文献 20致谢 211前言1.1乳腺癌与肿瘤酸性微环境癌症是目前为止影响人类健康的主要疾病，其中乳腺癌（BC）作为女性群体中的常见癌症，其致死率呈现增长趋势。乳腺癌的治疗手段包括手术、化疗等，但存在较多副作用，且患者预后差。临床常见的乳腺癌化疗药物包括紫杉醇（PTX）、阿霉素（DOX）、铂类等，然而存在心脏毒性、骨髓抑制、肾损伤等长期毒性，并缺乏靶向性，且易产生耐药性，严重限制了其临床疗效。近年来，出现了许多新型药物用于治疗乳腺癌。免疫检查点抑制剂，如帕博利珠单抗，阻断PD-1/PD-L1等免疫抑制信号，激活全身性免疫反应，使得T细胞恢复杀伤肿瘤细胞。此外抗体偶联药物如曲妥珠单抗，可以将抗体和化疗药相结合，通过抗体识别肿瘤表面抗原如人类表皮生长因子受体2（HER2），将药物靶向递送到肿瘤细胞，但此类药物要求肿瘤细胞特定抗原的高度表达，缺乏普适性，并存在骨髓抑制等毒性。因此，发掘在疗效高的同时毒性相对较低、不易发生耐药性且成本合适的乳腺癌治疗药物成为当今研究热门。肿瘤微环境（TME）是由肿瘤细胞与周围各种细胞、血管、细胞外基质（ECM）等共同组成的复杂生态系统ADDINZOTERO_ITEMCSL_CITATION{"citationID":"SJkv14er","properties":{"formattedCitation":"\\super[1]\\nosupersub{}","plainCitation":"[1]","noteIndex":0},"citationItems":[{"id":1669,"uris":["/users/15246511/items/ZGAXX7BL"],"itemData":{"id":1669,"type":"article-journal","abstract":"Thetumormicroenvironment(TME)influencestumorgrowth,metastaticspreadandresponsetotreatment.Oftenimmunosuppression,mediatedbytheTME,impairsabeneficialresponse.Thecomplexityofthetumorcompositionchallengesourabilitiestodesignnewandmoreeffectivetherapies.Goingforwardwewillneedto'manage'thecontentandorfunctionalityoftheTMEtoimprovetreatmentoutcomes.Currently,severaldifferentkindsoftreatmentsareavailabletopatientswithcancer:therearethetraditionalapproachesofchemotherapy,radiationandsurgery;therearetargetedagentsthatinhibitkinasesassociatedwithoncogenicpathways;therearemonoclonalantibodiesthattargetsurfaceantigensoftendeliveringtoxicpayloadsorcellsandfinallythereareantibodiesandbiologicsthatseektoovercometheimmunosuppressioncausedbyelementswithintheTME.HoweachofthesetherapiesinteractwiththeTMEiscurrentlyunderintenseandwidespreadinvestigation.InthisreviewwedescribehowtheTMEanditsimmunosuppressivecomponentscaninfluencebothtumorprogressionandresponsetotreatmentfocusingonthreeparticulartumortypes,classicHodgkinLymphoma(cHL),PancreaticDuctalAdenocarcinoma(PDAC)andGlioblastomaMultiforme(GBM).And,finally,weofferfiveapproachestomanipulateormanagetheTMEtoimproveoutcomesforcancerpatients.","call-number":"2","container-title":"FrontiersinImmunology","DOI":"10.3389/fimmu.2022.954992","ISSN":"1664-3224","journalAbbreviation":"Front.Immunol.","language":"eng","note":"PMID:36341428\nPMCID:PMC9630343","page":"954992","source":"5.7","title":"ManagingtheTMEtoimprovetheefficacyofcancertherapy","volume":"13","author":[{"family":"Bilotta","given":"MariaTeresa"},{"family":"Antignani","given":"Antonella"},{"family":"Fitzgerald","given":"DavidJ."}],"issued":{"date-parts":[["2022"]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[1]。与正常组织的pH7.2-7.4不同，肿瘤微环境呈现酸性，pH在6.5-6.9。另外肿瘤细胞在非缺氧状态下仍优先选择糖酵解这种无氧代谢方式，这种独特的代谢方式被称为瓦伯格效应（Warburgeffect）ADDINZOTERO_ITEMCSL_CITATION{"citationID":"JOVFrbwn","properties":{"formattedCitation":"\\super[2]\\nosupersub{}","plainCitation":"[2]","noteIndex":0},"citationItems":[{"id":1672,"uris":["/users/15246511/items/XMT8JT3B"],"itemData":{"id":1672,"type":"article-journal","abstract":"Cancercellsrewiretheirmetabolismtopromotegrowth,survival,proliferation,andlong-termmaintenance.Thecommonfeatureofthisalteredmetabolismistheincreasedglucoseuptakeandfermentationofglucosetolactate.Thisphenomenonisobservedeveninthepresenceofcompletelyfunctioningmitochondriaand,together,isknownasthe'WarburgEffect'.TheWarburgEffecthasbeendocumentedforover90yearsandextensivelystudiedoverthepast10years,withthousandsofpapersreportingtohaveestablishedeitheritscausesoritsfunctions.Despitethisintenseinterest,thefunctionoftheWarburgEffectremainsunclear.Here,weanalyzeseveralproposedexplanationsforthefunctionofWarburgEffect,emphasizetheirrationale,anddiscusstheircontroversies.","call-number":"1","container-title":"TrendsinBiochemicalSciences","DOI":"10.1016/j.tibs.2015.12.001","ISSN":"0968-0004","issue":"3","journalAbbreviation":"TrendsBiochem.Sci.","language":"en","note":"PMID:26778478\nPMCID:PMC4783224","page":"211-218","source":"11.6","title":"Thewarburgeffect:howdoesitbenefitcancercells?","title-short":"Thewarburgeffect","volume":"41","author":[{"family":"Liberti","given":"MariaV."},{"family":"Locasale","given":"JasonW."}],"issued":{"date-parts":[["2016",3]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[2]。糖酵解过程中产生大量乳酸，乳酸在排出肿瘤细胞时同时将H+释放到胞外。为平衡肿瘤细胞内的酸碱度，质子泵将H+释放到肿瘤微环境中。此外，肿瘤微环境中血管新生导致血管密度大且曲折，细胞外基质结构致密，这种异常的结构进一步导致了微环境局部缺氧和酸环境形成。然而酸性环境有益于肿瘤细胞生存、增殖、转移，并抑制免疫系统发挥作用，从而降低了药物疗效，阻碍了癌症治疗ADDINZOTERO_ITEMCSL_CITATION{"citationID":"DFndxz4n","properties":{"formattedCitation":"\\super[3]\\nosupersub{}","plainCitation":"[3]","noteIndex":0},"citationItems":[{"id":1675,"uris":["/users/15246511/items/CGDAUALM"],"itemData":{"id":1675,"type":"article-journal","abstract":"Mammaliancellsproduceenergybyoxidativephosphorylationunderaerobicconditions.However,inthe1920s,OttoWarburgreportedtheso-called\"Warburgeffect\"inwhichcancercellsproduceATPthatisbiasedtowardglycolysisratherthanmitochondrialoxidativephosphorylationnotonlyinanaerobicenvironmentbutalsoinaerobicenvironment.Glucoseisconvertedintolactatewithoutgoingintomitochondriaafterbeingmetabolizedinglycolysis.Comparedwithoxidativephosphorylation,theglycolysishasafasterATPproductionratebutitisveryinefficient,resultingincancercellsconsumingalargeamountofglucose.Increasedglucosemetabolismhasbecomeabiomarkerforcancercellsandhasledtothedevelopmentofpositronemissiontomographywithfluorodeoxyglucose.Tilldate,theWarburgeffecthasbeenaninefficientsystemforcancercellswithregardtoefficientenergyproduction,butsincetheconsumptionofoxygencanbesuppressedasthetumorgrowsinmass,itisthoughtthattheWarburgeffectisadvantageousinthissituationwhereinthetumorcanincreasedespitethelackofvessels.Inaddition,anincreasedlactatebytheglycolysiscausesacidosisinthemicroenvironmentoftissues,whichisthoughttodamagethesurroundingnormaltissuesandfavortheinvasionandmetastasisofcancer.Thus,Warburgeffectisoneofthekeymechanismsforcancerdevelopmentandwillbethenextpromisingtarget.Inthisreview,weintroducekeyplayersthatcanbetargetedintheWarburgeffectandoutlinetheprospectsoftreatment,targetingtheWarburgeffectingynecologicalcancer.","container-title":"JournalofObstetricsandGynaecologyResearch","DOI":"10.1111/jog.13867","ISSN":"1447-0756","issue":"3","journalAbbreviation":"J.Obstet.Gynaecol.Res.","language":"en","note":"PMID:30511455","page":"542-548","source":"PubMed","title":"Warburgeffectingynecologiccancers","volume":"45","author":[{"family":"Kobayashi","given":"Yusuke"},{"family":"Banno","given":"Kouji"},{"family":"Kunitomi","given":"Haruko"},{"family":"Takahashi","given":"Takayuki"},{"family":"Takeda","given":"Takashi"},{"family":"Nakamura","given":"Kanako"},{"family":"Tsuji","given":"Kosuke"},{"family":"Tominaga","given":"Eiichiro"},{"family":"Aoki","given":"Daisuke"}],"issued":{"date-parts":[["2019",3]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[3]。1.2黄芩苷清热解毒类中药是指具有清热、解毒、抗炎、抗肿瘤、抗病毒等作用的中药。研究者们发现，清热解毒类中药在治疗乳腺癌方面发挥独特作用。具有乳腺癌防治作用的清热解毒类中药包括穿心莲、夏枯草、黄芩、半枝莲、苦参、蒲公英等。蒲公英的根细胞提取物可以通过内源性线粒体凋亡途径激活半胱天冬蛋白酶-9（Caspase-9）和半胱天冬蛋白酶-3（Caspase-3）、下调B细胞淋巴瘤2（Bcl-2）表达，诱导乳腺癌MDA-MB-231细胞凋亡；蒲公英黄酮可以降低乳腺癌MCF-7细胞中的基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）蛋白表达，从而抑制细胞外基质（ECM）和基底膜（BM）降解，抑制肿瘤细胞逃逸、血管生成和转移，此外细胞划痕愈合率与穿膜细胞数量明显降低，进一步说明蒲公英黄酮可以抑制肿瘤细胞迁移，从而抑制肿瘤转移扩散ADDINZOTERO_ITEMCSL_CITATION{"citationID":"qXFpuwCh","properties":{"formattedCitation":"\\super[4]\\nosupersub{}","plainCitation":"[4]","noteIndex":0},"citationItems":[{"id":1624,"uris":["/users/15246511/items/RYGY48TY"],"itemData":{"id":1624,"type":"article-journal","abstract":"癌症已成为全球第二大致死病因，寻找抗肿瘤新药、阐明药物抗肿瘤分子机制是解决目前临床癌症治疗困难的有效策略。中药具有多种有效成分，因其不良反应小，且具有多靶点、多途径等优势而成为抗肿瘤药物研发的重要来源及研究热点。蒲公英具有清热解毒、消肿散结等功效，传统中医临床实践和现代中药药理学研究均表明蒲公英具有显著的抗肿瘤作用，能够抑制乳腺癌、肺癌、肝癌等多种癌症的发生发展。通过整合近年来国内外相关文献，对蒲公英的化学成分组成和有效成分的提取以及有效成分抗肿瘤的作用机制进行综述，为临床新型高效低毒抗癌药物研发提供药理学依据及科学参考。","call-number":"12-1108/R","container-title":"中草药","ISSN":"0253-2670","issue":"10","journalAbbreviation":"中草药","language":"zh","note":"CNKICite:28","page":"3391-3400","title":"蒲公英中有效成分抗肿瘤作用机制的研究进展","volume":"54","author":[{"family":"刘晓燕","given":""},{"family":"龙凤","given":""},{"family":"赵玉","given":""},{"family":"李雪","given":""},{"family":"叶海琳","given":""},{"family":"周旋","given":""}],"issued":{"date-parts":[["2023"]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[4]。Wnt/β-catenin信号通路异常激活，促进上皮-间充质转化（EMT）并提高癌症干细胞（CSC）活性，促进乳腺癌细胞的生长、转移并与耐药相关，研究表明，清热解毒中药活性成分如穿心莲内酯、黄芩素等通过干扰Wnt/β-catenin信号通路，抑制癌细胞的生长、增殖和转移，抑制乳腺癌的发展ADDINZOTERO_ITEMCSL_CITATION{"citationID":"UAzYvMJ2","properties":{"formattedCitation":"\\super[5]\\nosupersub{}","plainCitation":"[5]","noteIndex":0},"citationItems":[{"id":1626,"uris":["/users/15246511/items/WZF6YK9A"],"itemData":{"id":1626,"type":"document","title":"中药调控Wnt_β-cat...号通路干预乳腺癌的研究进展_凌璐"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[5]。穿心莲内酯（Andro）还可以诱导Hippo通路中的下游YAP蛋白磷酸化，从而降低三阴性乳腺癌（TNBC）细胞中的YAP和ANKRD1蛋白表达量，抑制肿瘤细胞增殖和干细胞分化，并促进细胞凋亡，这可能是穿心莲内酯（Andro）发挥抗乳腺癌作用的的作用机制之一ADDINZOTERO_ITEMCSL_CITATION{"citationID":"sgc0QP7P","properties":{"formattedCitation":"\\super[6]\\nosupersub{}","plainCitation":"[6]","noteIndex":0},"citationItems":[{"id":1628,"uris":["/users/15246511/items/WAJ4K3NZ"],"itemData":{"id":1628,"type":"article-journal","abstract":"目的通过体内外实验，探讨穿心莲内酯（andrographolide,Andro）对三阴性乳腺癌细胞增殖、迁移、干细胞特性和上皮间质转化进程的影响及可能作用机制。方法利用磺酰罗丹明B（sulforhodamineB,SRB）比色法检测细胞活性；采用细胞划痕实验、流式技术和干细胞成球实验检测细胞迁移能力、干细胞增殖能力及CD44⁺/CD24^-/low的比例；WesternBlot实验检测NESTIN、NANOG、E-cadherin、Vimentin、N-cadherin、Fibronectin、p-YAP、YAP、ANKRD1蛋白的表达。采用小鼠移植瘤实验检测Andro对乳腺癌细胞体内增殖和小鼠致瘤性的作用。利用免疫组化实验检测各组肿瘤组织中YAP和ANKRD1的表达。结果体外实验结果表明：Andro可剂量依赖性降低MDA-MB-231和4T1细胞活性；与对照组比较，经Andro干预后的MDA-MB-231和4T1细胞的划痕愈合率降低，CD44⁺/CD24^-/low比例下降，干细胞微球的体积减小和数量降低（P<0.05）,NESTIN、NANOG、Vimentin、N-cadherin、Fibronectin、YAP和ANKRD1蛋白表达下降，而E-cadherin和p-YAP的表达上升。体内实验结果表明：与对照组相比，经Andro干预的小鼠肿瘤体积和肿瘤质量减小，肿瘤组织中YAP和ANKRD1的表达下降（P<0.01）。结论Andro可通过调控Hippo/YAP信号通路发挥抗三阴性乳腺癌的作用。","call-number":"44-1193/R","container-title":"实用医学杂志","ISSN":"1006-5725","issue":"16","journalAbbreviation":"实用医学杂志","language":"zh","note":"CNKICite:4","page":"2050-2056","title":"基于Hippo/YAP信号通路探讨穿心莲内酯抗三阴性乳腺癌的作用机制","volume":"39","author":[{"family":"黄翠霞","given":""},{"family":"张雅倩","given":""},{"family":"杨爱萍","given":""},{"family":"刘芮含秋","given":""},{"family":"路艳","given":""}],"issued":{"date-parts":[["2023"]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[6]。西黄丸具有清热解毒散痈作用，临床常用于治疗乳腺癌，在乳腺癌MCF-7细胞和MDA-MB-231细胞中，西黄丸下调STAT3活性，抑制表皮生长因子（EGF）所诱导的上皮-间充质转化（EMT）过程，并抑制细胞中的免疫检查点PD-L1蛋白表达，同时上调单核细胞经典群中HLA-DR表达，综上说明，清热解毒中药西黄丸可以抑制乳腺癌细胞EMT并提高机体对乳腺癌细胞的杀伤能力ADDINZOTERO_ITEMCSL_CITATION{"citationID":"DX7vImSW","properties":{"formattedCitation":"\\super[7]\\nosupersub{}","plainCitation":"[7]","noteIndex":0},"citationItems":[{"id":1631,"uris":["/users/15246511/items/MLA22J9C"],"itemData":{"id":1631,"type":"thesis","abstract":"西黄丸由牛黄(原方犀黄)、麝香、乳香、没药四味药物组成,首见于清代名医王洪绪《外科证治全生集》。具有和营消肿止痛,清热解毒散痈的作用,可用于治疗热毒蕴结所致的多种恶疾(如流注、乳岩、痰核、瘰疬、肺痈、小肠痈等)。现代临床上可用来治疗乳腺癌、宫颈癌等多种肿瘤,但分子机制有待阐明。复发转移是乳腺癌治疗失败的主要原因。上皮间质转化(Epithelialmesenchymaltransition,EMT)与肿瘤转移密切相关。EMT经过一系列生物学变化,丧失细胞极性和细胞间接触能力,增强了运动和侵袭能力,进而赋予了癌细胞侵袭和转移能力。在EMT过程中,上皮标志物如E钙黏素蛋白(E-cadherin)、角蛋白(Cytokeratin)等表达水平降低,间质标志物如纤连蛋白(Fibronectin)、N钙黏素蛋白(N-cadherin)、波形蛋白(Vimentin)等表达水平升高。表皮生长因子(EpidermalGrowthFactor,EGF)与其受体结合后,可诱导E-cadherin进入胞内,上调Snail1或Twist的表达水平,下调E-cadherin的表达,诱导EMT表型,进而参与肿瘤的增殖、迁移、侵袭和转移。EMT状态和程序性死亡配体1(programmeddeathligand1,PD-L1)信号之间存在复杂的双向调节作用。EMT与PD-L1高表达有关:EMT相关标志物如Snail和波形蛋白(Vimentin)H评分与PD-L1表达呈正相关。PD-L1的高表达通常被认为是癌症患者预后不良的预测因子,癌细胞可通过自身高表达PD-L1来逃避宿主的抗癌免疫攻击。PD-L1可与活化的T细胞表面表达的程序性死亡受体1(Programmeddeathreceptor1,PD-1)相互作用,诱导T细胞凋亡,导致肿瘤免疫逃逸。除EMT与PD-L1有重要的双向调节作用之外,PD-L1还受到γ-干扰素(Interferon-γ,IFN-y)的上调。肿瘤细胞内干扰素刺激基因高表达往往会发生化疗或免疫治疗的耐药。IFN-y与其受体结合后,激活下游JAK/STAT信号通路,IRF-1蛋白表达激活,进而诱导肿瘤细胞PD-L1的表达;而另一个干扰素刺激基因IFIT3过表达可直接促进肿瘤耐药,而敲除IFIT3基因后可减弱化疗耐药性;在乳腺癌患者中,干扰素下游的OAS1的表达也与预后不良密切相关。尽管免疫细胞中高表达的具有IFN-γ...","genre":"硕士学位论文","language":"zh","note":"CNKICite:3","publisher":"中国中医科学院","title":"西黄丸抑制乳腺癌上皮间质转化和免疫逃逸的分子机制","author":[{"family":"杨忖卿","given":""}],"issued":{"date-parts":[["2021"]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[7]。黄芩苷（BA）是一种提取自清热解毒类唇形科双子叶植物黄芩ScutellariabaicalensisGeorgi的干燥根中的黄酮类化合物，是黄芩素与葡萄糖醛酸形成的糖苷。黄芩苷具有清热、解毒、保肝利胆、抗菌、抗炎、抗病毒、抗氧化等作用ADDINZOTERO_ITEMCSL_CITATION{"citationID":"n41fjVCg","properties":{"formattedCitation":"\\super[8\\uc0\\u8211{}10]\\nosupersub{}","plainCitation":"[8–10]","noteIndex":0},"citationItems":[{"id":1638,"uris":["/users/15246511/items/YIVRMDVN"],"itemData":{"id":1638,"type":"article-journal","abstract":"黄芩苷是从唇形科双子叶植物黄芩Scutellariabaicalensis的干燥根中提取分离出来的一种黄酮类化合物，对黄芩苷的药理作用及机制研究的关注度越来越高，主要具有抗病毒、抗肿瘤、抗炎、抗菌、神经保护、抗氧化等药理活性，还具有抗抑郁、调节免疫、安胎、降压、镇痛等药理作用。为更充分开发黄芩苷的药用价值，对黄芩苷的主要药理活性和相关作用机制进行分类整理，旨在为黄芩苷的临床应用及新药研发提供科学依据。","container-title":"药物评价研究","issue":"11","journalAbbreviation":"药物评价研究","language":"zh","note":"foundation:国家自然科学基金资助项目（82360816）；贵州省中医药管理局中医药、民族医药科学技术研究专项课题（QZYY-2024-188,QZYY-2021-084）；贵州省中药炮制技术传承基地建设国家中医药科技项目[（2015）86号]；贵州中医药大学研究生教育创新计划项目（YCXKYS2023034）；\ndownload:1930\nalbum:医药卫生科技\nCLC:R285\ndbcode:CJFQ\ndbname:CJFDLAST2024\nfilename:YWPJ202411025","page":"2688-2696","source":"CNKI","title":"黄芩苷药理活性和作用机制研究进展","volume":"47","author":[{"literal":"侯晓杰"},{"literal":"张建锋"},{"literal":"侯长周"},{"literal":"周礼杰"},{"literal":"代华"},{"literal":"张石宇"},{"literal":"李玮"}],"issued":{"date-parts":[["2024"]]}}},{"id":1636,"uris":["/users/15246511/items/D2RZEXSB"],"itemData":{"id":1636,"type":"article-journal","abstract":"目的:建立清热解毒口服液中黄芩苷的含量测定方法。方法:高效液相色谱法,采用AgilentZORBAXSB-C18(250×4.6mm,5μm)色谱柱;以甲醇-水-磷酸(50:50:0.3)为流动相;流速0.8mL/min;检测波长为276nm。结果:在4.0259μg/mL～80.5176μg/mL浓度范围内黄芩苷的浓度和峰面积具有良好的线性关系,R=0.99999;平均回收率为99.99%,RSD=0.57%(n=9)。结论:本方法准确、可靠、重复性好,适用于清热解毒口服液中黄芩苷的含量控制。","container-title":"科学技术创新","issue":"24","journalAbbreviation":"科学技术创新","language":"zh","note":"download:409\nalbum:基础科学;工程科技Ⅱ辑;医药卫生科技\nCLC:R286.0\ndbcode:CJFQ\ndbname:CJFDLAST2020\nfilename:HLKX202024012","page":"19-20","source":"CNKI","title":"高效液相色谱法测定清热解毒口服液中黄芩苷的含量","author":[{"literal":"张巍"}],"issued":{"date-parts":[["2020"]]}}},{"id":1640,"uris":["/users/15246511/items/HQMPV4IE"],"itemData":{"id":1640,"type":"article-journal","abstract":"黄芩苷和黄芩素都是从黄芩的干燥根中提取的主要的黄酮类成分。国内外学者大量研究表明,两者均具有保肝、利胆、抗肿瘤、抗菌、抗炎、抗抑郁、抗氧化等药理作用。文章在查阅最新相关文献的基础上,对黄酮类化合物黄芩苷与黄芩素的药理作用及机制进行了综述,以期为黄芩苷及黄芩素的临床研究与应用提供理论依据,同时为它们在食品、保健品、化妆品、药品等行业的开发提供参考。","container-title":"时珍国医国药","issue":"4","journalAbbreviation":"时珍国医国药","language":"zh","note":"foundation:国家自然科学基金(81160413)；贵州省科技厅项目(黔科合成转字[2015]5213号)；\ndownload:4712\nalbum:医药卫生科技\nCLC:R285.5\ndbcode:CJFQ\ndbname:CJFDLAST2020\nfilename:SZGY202004048","page":"921-925","source":"CNKI","title":"黄芩苷与黄芩素药理作用及机制研究进展","volume":"31","author":[{"literal":"朱亚南"},{"literal":"杨七妹"},{"literal":"张硕"},{"literal":"张敏"},{"literal":"高秀丽"}],"issued":{"date-parts":[["2020"]]}}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[8–10]。黄芩苷在抗肿瘤方面也发挥着一定作用，尤其是乳腺癌ADDINZOTERO_ITEMCSL_CITATION{"citationID":"FSkydzdi","properties":{"formattedCitation":"\\super[10]\\nosupersub{}","plainCitation":"[10]","noteIndex":0},"citationItems":[{"id":1640,"uris":["/users/15246511/items/HQMPV4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