口服納米抗氧化劑用于腸道炎癥的治療作用摘要炎癥性腸?。↖BD）是一種由免疫介導(dǎo)的慢性復(fù)發(fā)性腸道疾病，全球患病人數(shù)超過500萬，已成為世界上第3大常見疾病。當前治療藥物（小分子藥物、抗生素和抗體）取得了一定療效，然而，長期使用可能導(dǎo)致嚴重的并發(fā)癥、抗生素耐藥性和不良的免疫反應(yīng)?；诩{米顆粒的靶向給藥系統(tǒng)近年取得顯著進展，有望提升療效，改善腸道炎癥，并降低副作用風(fēng)險。本研究設(shè)計開發(fā)了一種口服納米氧化劑Cur-Ce@FTA，利用單寧酸（TA）與聚醚F127自組裝行為形成姜黃素（Cur）與氧化鈰包埋的納米組裝體，以提高其溶解度并可能增強其生物活性，使其更有效地到達腸道病變部位發(fā)揮作用。Cur-Ce@FTA能保持對炎癥結(jié)腸的良好靶向能力，這主要歸因于帶負電荷的單寧酸和帶正電荷的炎癥上皮細胞之間的靜電相互作用。CeO2納米材料的生物醫(yī)學(xué)應(yīng)用潛力主要源于其模擬天然酶的抗氧化特性，包括過氧化氫酶（CAT）、過氧化物酶（POD）和超氧化物歧化酶（SOD）樣活性。這種多酶仿生特性使其能夠高效清除自由基及活性氧（ROS），從而有效保護生物系統(tǒng)免受氧化損傷，在IBD的抗氧化及抗炎治療中潛力顯著，同時利用姜黃素強大的抗氧化特性，協(xié)同發(fā)揮治療作用，達到長期治療IBD的目的。關(guān)鍵詞：炎癥性腸病納米抗氧化劑姜黃素氧化鈰單寧酸第一章緒論1.1腸道炎癥的研究背景1.1.1腸道炎癥的簡介炎癥性腸病（Inflammatoryboweldisease，IBD）是免疫反應(yīng)介導(dǎo)的慢性緩解和復(fù)發(fā)性腸病的總稱，是一種慢性復(fù)發(fā)性和緩解性疾病，全球患病人數(shù)超過500萬，已成為世界上第3大常見疾病ADDINEN.CITEADDINEN.CITE.DATA[1]。IBD分為克羅恩?。–D）和潰瘍性結(jié)腸炎（UC）ADDINEN.CITEADDINEN.CITE.DATA[2,3]。CD病變范圍廣泛，可累及整個消化道，表現(xiàn)為腸道炎癥和潰瘍，并伴有肉芽腫形成ADDINEN.CITE<EndNote><Cite><Author>Zhou</Author><Year>2023</Year><RecNum>144</RecNum><DisplayText><styleface="superscript">[4]</style></DisplayText><record><rec-number>144</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1715246051">144</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhou,Feini</author><author>Mai,Ting</author><author>Wang,Ziren</author><author>Zeng,Zhaolong</author><author>Shi,Jingjing</author><author>Zhang,Fan</author><author>Kong,Ning</author><author>Jiang,Hao</author><author>Guo,Lingnan</author><author>Xu,Maosheng</author><author>Lin,Jiangnan</author></authors></contributors><auth-address>ZhejiangChineseMedUniv,SchClinMed1,Hangzhou,PeoplesRChina ZhejiangChineseMedUniv,AffiliatedHosp1,ZhejiangProvHospChineseMed,DeptRadiol,54YoudianRd,Hangzhou,PeoplesRChina ZhejiangChineseMedUniv,SchClinMed3,Hangzhou,PeoplesRChina</auth-address><titles><title>Theimprovementofintestinaldysbiosisandhepaticmetabolicdysfunctionindextransulfatesodium-inducedcolitismice:effectsofcurcumin</title><secondary-title>JOURNALOFGASTROENTEROLOGYANDHEPATOLOGY</secondary-title></titles><periodical><full-title>JOURNALOFGASTROENTEROLOGYANDHEPATOLOGY</full-title></periodical><pages>1333-1345</pages><volume>38</volume><number>8</number><dates><year>2023</year><pub-dates><date>2023AUG</date></pub-dates></dates><isbn>0815-9319 1440-1746</isbn><accession-num>WOS:000990196800001</accession-num><work-type>Article</work-type><urls></urls><custom6>MAY2023</custom6><electronic-resource-num>10.1111/jgh.16205</electronic-resource-num><access-date>2023-05-28</access-date></record></Cite></EndNote>[4]，UC可使結(jié)腸腸道菌群紊亂和腸道屏障功能嚴重破壞，一般只發(fā)生在結(jié)腸部位，只涉及黏膜和黏膜下層，其結(jié)腸鏡檢查結(jié)果是假性息肉和連續(xù)的炎癥區(qū)域。雖然CD和UC在多種方面有較大差異，但它們在癥狀上表現(xiàn)出類似性，包括腹痛、腹瀉、腸外表現(xiàn)和營養(yǎng)不良等，部分患者還會伴有關(guān)節(jié)炎、口腔潰瘍及皮炎等癥狀A(yù)DDINEN.CITE<EndNote><Cite><Author>王佳俊</Author><Year>2021</Year><RecNum>148</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>148</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1716035020">148</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author><styleface="normal"font="default"charset="134"size="100%">王佳俊</style><styleface="normal"font="default"size="100%">,</style><styleface="normal"font="default"charset="134"size="100%">陳青垚</style><styleface="normal"font="default"size="100%">,</style><styleface="normal"font="default"charset="134"size="100%">王建</style><styleface="normal"font="default"size="100%">,</style><styleface="normal"font="default"charset="134"size="100%">等</style></author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">基于數(shù)據(jù)挖掘和網(wǎng)絡(luò)藥理</style><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">學(xué)探究含黃連方劑治療潰瘍性結(jié)腸炎的配伍規(guī)律及作</style><styleface="normal"font="default"size="100%"></style><styleface="normal"font="default"charset="134"size="100%">用機制</style><styleface="normal"font="default"size="100%">[J]</style></title><secondary-title><styleface="normal"font="default"charset="134"size="100%">中草藥</style><styleface="normal"font="default"size="100%">,2021,52(19):5984-5995.</style></secondary-title></titles><periodical><full-title>中草藥,2021,52(19):5984-5995.</full-title></periodical><dates><year>2021</year></dates><urls></urls></record></Cite></EndNote>[5]。IBD的確切病因尚不清楚，但目前認為IBD的發(fā)病機制與氧化應(yīng)激、炎癥介質(zhì)增多、破壞黏膜屏障、腸道微生物菌群以及免疫反應(yīng)有關(guān)ADDINEN.CITEADDINEN.CITE.DATA[6,7]。IBD病程的延長與結(jié)直腸癌的發(fā)生和發(fā)展密切相關(guān)，并且對患者的身體、心理和社會的某些方面都造成很大的影響，通常會導(dǎo)致患者的抑郁和焦慮情緒ADDINEN.CITEADDINEN.CITE.DATA[8]。因此，研究IBD的治療方法對于保障患者的生活質(zhì)量至關(guān)重要。目前，氨基水楊酸鹽、皮質(zhì)類固醇、免疫抑制劑、生物制劑和抗生素等藥物已被廣泛用于治療IBD，然而，此類治療方法存在生物利用度低和系統(tǒng)副作用大的問題，如長期攝入這些藥物會對患者產(chǎn)生嚴重的不良反應(yīng)ADDINEN.CITE<EndNote><Cite><Author>Pithadia</Author><Year>2011</Year><RecNum>123</RecNum><DisplayText><styleface="superscript">[9]</style></DisplayText><record><rec-number>123</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1714560255">123</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Pithadia,A.B.</author><author>Jain,S.</author></authors></contributors><auth-address>DepartmentofPharmacology,L.M.CollegeofPharmacy,Navrangpura,Ahmedabad-380009Gujarat,India.abpithadia@</auth-address><titles><title>Treatmentofinflammatoryboweldisease(IBD)</title><secondary-title>PharmacolRep</secondary-title></titles><periodical><full-title>PharmacolRep</full-title></periodical><pages>629-42</pages><volume>63</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Anti-InflammatoryAgents/adverseeffects/therapeuticuse</keyword><keyword>Colitis,Ulcerative/*drugtherapy/physiopathology</keyword><keyword>CrohnDisease/*drugtherapy/physiopathology</keyword><keyword>*DrugDeliverySystems</keyword><keyword>Glucocorticoids/adverseeffects/therapeuticuse</keyword><keyword>Humans</keyword><keyword>ImmunologicFactors/adverseeffects/pharmacology/therapeuticuse</keyword><keyword>ImmunosuppressiveAgents/adverseeffects/therapeuticuse</keyword></keywords><dates><year>2011</year></dates><isbn>1734-1140</isbn><accession-num>21857074</accession-num><urls></urls><electronic-resource-num>10.1016/s1734-1140(11)70575-8</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[9]：急性胰腺炎、腸道菌群失衡、肝功能損傷和骨質(zhì)疏松癥等。所以迫切需要開發(fā)有較好療效且不良反應(yīng)較小的靶向治療藥物和方法ADDINEN.CITE<EndNote><Cite><Author>GodatS</Author><Year>2018</Year><RecNum>149</RecNum><DisplayText><styleface="superscript">[10,11]</style></DisplayText><record><rec-number>149</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1716035343">149</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>GodatS,FournierN,SafroneevaE,etal.</author></authors></contributors><titles><title>Frequencyandtypeofdrug-relatedsideeffectsnecessitatingtreatmentdiscontinuationintheswissinflammatoryboweldiseasecohort.</title><secondary-title>EurJGastroenterolHepatol,2018,30(6):612-620.</secondary-title></titles><periodical><full-title>EurJGastroenterolHepatol,2018,30(6):612-620.</full-title></periodical><dates><year>2018</year></dates><urls></urls></record></Cite><Cite><Author>MaXW</Author><Year>2018</Year><RecNum>150</RecNum><record><rec-number>150</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1716035625">150</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>MaXW,HuYC,LiX,etal.</author></authors></contributors><titles><title>Periplanetaamericanaamelioratesdextransulfatesodium-inducedulcerativecolitisinratsbyKeap1/Nrf-2activation,intestinalbarrierfunction,andgutmicrobiotaregulation.</title><secondary-title>FrontPharmacol,2018,9:944.</secondary-title></titles><periodical><full-title>FrontPharmacol,2018,9:944.</full-title></periodical><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>[10,11]。近年來，基于納米顆粒的靶向給藥系統(tǒng)在IBD治療方面取得了顯著進展，有望提高治療效果，減少副作用。1.1.2ROS與氧化應(yīng)激氧氣代謝是哺乳動物細胞生存所不可或缺的環(huán)節(jié)，該過程會產(chǎn)生活性氧（ROS）。ROS包含自由基類物質(zhì)（如超氧陰離子?O2-、羥自由基?OH）和非自由基類物質(zhì)（如過氧化氫H2O2、單線態(tài)氧1O2）。此外，次氯酸HOCl、氯胺RNHCl及臭氧O3等也屬于ROS范疇。另一類重要活性分子是活性氮族（RNS），其代表物有一氧化氮?NO、二氧化氮?NO2，以及過氧亞硝酸鹽ONOO-、三氧化二氮N2O3等非自由基化合物。ROS和RNS都是負責(zé)細胞內(nèi)碳水化合物、蛋白質(zhì)、脂質(zhì)和核酸損傷的主要媒介，并且它們都具有不配對電子的不穩(wěn)定性，因此具有高度的反應(yīng)性和活性。據(jù)報道，ROS和RNS可上調(diào)參與消化道先天和適應(yīng)性免疫反應(yīng)的基因的表達ADDINEN.CITEADDINEN.CITE.DATA[12]。當ROS和自由基的細胞毒性作用超過了抗氧化劑對其細胞毒性作用的消除，就會產(chǎn)生氧化應(yīng)激進而導(dǎo)致組織損傷ADDINEN.CITEADDINEN.CITE.DATA[13,14]。在生理狀態(tài)下，細胞內(nèi)ROS水平通過嚴格的動態(tài)平衡機制維持于極低濃度范圍，這對保障細胞正常功能至關(guān)重要。然而，當ROS過量累積時，會打破氧化還原穩(wěn)態(tài)，引發(fā)氧化應(yīng)激反應(yīng)。過量的ROS會攻擊和損傷幾乎所有的細胞成分，包括細胞膜、脂質(zhì)、蛋白質(zhì)、酶和DNA，并因此導(dǎo)致細胞凋亡ADDINEN.CITEADDINEN.CITE.DATA[15]。ROS對細胞膜的影響主要表現(xiàn)為由于細胞膜脂質(zhì)雙分子層中的多不飽和脂肪酸具有兩個或多個碳雙鍵的結(jié)構(gòu)，這種結(jié)構(gòu)易受到氧化攻擊，導(dǎo)致過氧化脂質(zhì)積累ADDINEN.CITE<EndNote><Cite><Author>曹?</Author><Year>2021</Year><RecNum>367</RecNum><DisplayText><styleface="superscript">[16]</style></DisplayText><record><rec-number>367</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1747660269">367</key></foreign-keys><ref-typename="Thesis">32</ref-type><contributors><authors><author>曹?</author></authors><tertiary-authors><author>焦擁政,</author></tertiary-authors></contributors><titles><title>基于ROS-MAPK-線粒體途徑探討補腎益精方治療少弱精子癥的作用機制</title></titles><keywords><keyword>少弱精子癥</keyword><keyword>補腎益精方</keyword><keyword>氧化應(yīng)激</keyword><keyword>p38MAPK信號通路</keyword><keyword>線粒體凋亡</keyword></keywords><dates><year>2021</year></dates><work-type>博士</work-type><urls><related-urls><url>/doi/10.27658/ki.gzzyy.2021.000038</url></related-urls></urls><electronic-resource-num>10.27658/ki.gzzyy.2021.000038</electronic-resource-num><remote-database-provider>Cnki</remote-database-provider></record></Cite></EndNote>[16]。而過氧化脂質(zhì)的積累加速了對細胞膜完整性的破壞，這種損傷和ROS增加導(dǎo)致跨膜酶、受體和其他膜蛋白失活，導(dǎo)致細胞膜破裂死亡。其次，作為細胞主要成分的蛋白質(zhì)和酶也是ROS氧化的目標，例如?OH自由基攻擊并破壞了許多蛋白質(zhì)和酶。?OH的氧化作用包括誘導(dǎo)蛋白質(zhì)構(gòu)象發(fā)生變化，這是導(dǎo)致蛋白質(zhì)功能部分或完全喪失的一個主要原因。ONOO-是一種由?O2-和?NO反應(yīng)快速形成的強有力的氧化劑和硝化物，它可與多種生物大分子（如蛋白質(zhì)）發(fā)生相互作用，誘導(dǎo)其發(fā)生氧化修飾或硝化反應(yīng)，最終引發(fā)細胞結(jié)構(gòu)損傷。此外，ROS會對DNA產(chǎn)生一定的影響，已知核DNA和線粒體DNA也是ROS氧化攻擊的目標，特別是來自?OH和ONOO-的攻擊，它們導(dǎo)致堿基甲基化、羥基化損傷以及雙鏈斷裂，從而導(dǎo)致三磷酸腺苷耗竭、基因突變和線粒體DNA缺失，這些變化最終誘發(fā)惡性轉(zhuǎn)化和細胞死亡。因此，ROS通過氧化應(yīng)激損傷了幾乎所有的細胞成分ADDINEN.CITE<EndNote><Cite><Author>Mittal</Author><Year>2014</Year><RecNum>361</RecNum><DisplayText><styleface="superscript">[17]</style></DisplayText><record><rec-number>361</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1746699893">361</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Mittal,M.</author><author>Siddiqui,M.R.</author><author>Tran,K.</author><author>Reddy,S.P.</author><author>Malik,A.B.</author></authors></contributors><auth-address>1DepartmentofPharmacology,CenterforLungandVascularBiology,UniversityofIllinoisCollegeofMedicine,Chicago,Illinois.</auth-address><titles><title>Reactiveoxygenspeciesininflammationandtissueinjury</title><secondary-title>AntioxidRedoxSignal</secondary-title></titles><periodical><full-title>AntioxidRedoxSignal</full-title></periodical><pages>1126-67</pages><volume>20</volume><number>7</number><edition>20131022</edition><keywords><keyword>Animals</keyword><keyword>Endothelium,Vascular/metabolism/*pathology</keyword><keyword>Humans</keyword><keyword>Inflammation/metabolism/*pathology</keyword><keyword>Neutrophils/metabolism/pathology</keyword><keyword>OxidativeStress/physiology</keyword><keyword>ReactiveOxygenSpecies/*metabolism</keyword></keywords><dates><year>2014</year><pub-dates><date>Mar1</date></pub-dates></dates><isbn>1523-0864(Print) 1523-0864</isbn><accession-num>23991888</accession-num><urls></urls><custom2>PMC3929010</custom2><electronic-resource-num>10.1089/ars.2012.5149</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[17]。雖然不受控制的氧化應(yīng)激會對機體造成損害，但內(nèi)源性抗氧化防御系統(tǒng)能夠有效調(diào)控ROS/RNS水平，確保其濃度得到控制，防止其積累至有害程度。這一保護體系主要包括：（1）胞內(nèi)抗氧化酶，如超氧化物歧化酶（SOD）、谷胱甘肽過氧化物酶（GPX）和過氧化氫酶（CAT）；（2）非酶類抗氧化分子（如還原型谷胱甘肽）；（3）胞外抗氧化物質(zhì)，例如維生素、礦物質(zhì)、磷脂及尿酸等ADDINEN.CITEADDINEN.CITE.DATA[18]。1.1.3ROS與IBD在IBD中，腸道黏膜活性氧（ROS）水平異常升高，其病理機制表現(xiàn)為多維度損傷：ROS通過直接破壞腸上皮細胞間緊密連接蛋白（如occludin）削弱腸道屏障完整性，導(dǎo)致病原體和抗原易位ADDINEN.CITEADDINEN.CITE.DATA[19]；同時激活NF-κB和NLRP3炎癥小體信號通路，促進TNF-α、IL-1β等促炎因子過度表達，驅(qū)動慢性炎癥惡化ADDINEN.CITE<EndNote><Cite><Author>Neurath</Author><Year>2014</Year><RecNum>236</RecNum><DisplayText><styleface="superscript">[20]</style></DisplayText><record><rec-number>236</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1746115552">236</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Neurath,M.F.</author></authors></contributors><auth-address>DepartmentofMedicine1,UniversityofErlangen-Nürnberg,KussmaulCampusforMedicalResearch,91054Erlangen,Germany.</auth-address><titles><title>Cytokinesininflammatoryboweldisease</title><secondary-title>NatRevImmunol</secondary-title></titles><periodical><full-title>NatRevImmunol</full-title></periodical><pages>329-42</pages><volume>14</volume><number>5</number><edition>20140422</edition><keywords><keyword>AdaptiveImmunity/immunology</keyword><keyword>Animals</keyword><keyword>Cytokines/*immunology</keyword><keyword>Humans</keyword><keyword>Immunity,Innate/immunology</keyword><keyword>InflammatoryBowelDiseases/*immunology</keyword></keywords><dates><year>2014</year><pub-dates><date>May</date></pub-dates></dates><isbn>1474-1733</isbn><accession-num>24751956</accession-num><urls></urls><electronic-resource-num>10.1038/nri3661</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[20]；此外，ROS的過度生成會選擇性抑制腸道共生菌生長，引發(fā)菌群失調(diào)并加劇免疫微環(huán)境紊亂ADDINEN.CITE<EndNote><Cite><Author>Grisham</Author><Year>1994</Year><RecNum>235</RecNum><DisplayText><styleface="superscript">[21]</style></DisplayText><record><rec-number>235</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1746115219">235</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Grisham,M.B.</author></authors></contributors><auth-address>DepartmentofPhysiologyandBiophysics,LouisianaStateUniversityMedicalCenter,Shreveport71130.</auth-address><titles><title>Oxidantsandfreeradicalsininflammatoryboweldisease</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title></periodical><pages>859-61</pages><volume>344</volume><number>8926</number><keywords><keyword>AminosalicylicAcids/pharmacology/therapeuticuse</keyword><keyword>Animals</keyword><keyword>FreeRadicals</keyword><keyword>Humans</keyword><keyword>InflammatoryBowelDiseases/*metabolism/prevention&control</keyword><keyword>Mesalamine</keyword><keyword>Oxygen/*metabolism</keyword><keyword>ReactiveOxygenSpecies/*metabolism</keyword></keywords><dates><year>1994</year><pub-dates><date>Sep24</date></pub-dates></dates><isbn>0140-6736(Print) 0140-6736</isbn><accession-num>7916405</accession-num><urls></urls><electronic-resource-num>10.1016/s0140-6736(94)92831-2</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[21]。研究表明，IBD患者結(jié)腸組織中超氧化物歧化酶（SOD）和過氧化氫酶（CAT）等抗氧化酶活性顯著降低，提示抗氧化系統(tǒng)功能缺陷是疾病進展的關(guān)鍵病理環(huán)節(jié)ADDINEN.CITE<EndNote><Cite><Author>Kruidenier</Author><Year>2003</Year><RecNum>238</RecNum><DisplayText><styleface="superscript">[22]</style></DisplayText><record><rec-number>238</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1746116065">238</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kruidenier,L.</author><author>Kuiper,I.</author><author>VanDuijn,W.</author><author>Mieremet-Ooms,M.A.</author><author>vanHogezand,R.A.</author><author>Lamers,C.B.</author><author>Verspaget,H.W.</author></authors></contributors><auth-address>DepartmentofGastroenterologyandHepatology,LeidenUniversityMedicalCenter,TheNetherlands.</auth-address><titles><title>Imbalancedsecondarymucosalantioxidantresponseininflammatoryboweldisease</title><secondary-title>JPathol</secondary-title></titles><periodical><full-title>JPathol</full-title></periodical><pages>17-27</pages><volume>201</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged,80andover</keyword><keyword>Antioxidants/*metabolism</keyword><keyword>Catalase/metabolism</keyword><keyword>Female</keyword><keyword>Glutathione/metabolism</keyword><keyword>GlutathionePeroxidase/metabolism</keyword><keyword>Humans</keyword><keyword>ImmunoenzymeTechniques</keyword><keyword>InflammatoryBowelDiseases/enzymology/*metabolism</keyword><keyword>IntestinalMucosa/enzymology/*metabolism</keyword><keyword>Male</keyword><keyword>Metallothionein/metabolism</keyword><keyword>MiddleAged</keyword><keyword>OxidativeStress</keyword><keyword>Peroxidase/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-3417(Print) 0022-3417</isbn><accession-num>12950013</accession-num><urls></urls><electronic-resource-num>10.1002/path.1408</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[22]。隨著UC的發(fā)展，結(jié)腸內(nèi)炎癥細胞異?；罨?，觸發(fā)促氧化劑分子生成增加。氧化應(yīng)激歸因于氧化還原失衡，而氧化還原失衡是ROS的過量生成和抗氧化系統(tǒng)清除能力不足引起的ADDINEN.CITEADDINEN.CITE.DATA[23,24]。過多的ROS產(chǎn)生導(dǎo)致細胞蛋白質(zhì)、脂質(zhì)和核酸的氧化損傷，從而導(dǎo)致一些細胞功能障礙，促使UC的發(fā)生發(fā)展。結(jié)腸上皮細胞雖含有多種抗氧化系統(tǒng)，如抗氧化酶，即谷胱甘肽（GSH）、谷胱甘肽過氧化物酶（GPX）和脂氧合酶（LOXs），但它們通常在UC病理條件下失調(diào)ADDINEN.CITEADDINEN.CITE.DATA[25,26]。因此，我們認為，通過消除ROS來改善促炎微環(huán)境這一方法在促進IBD黏膜愈合方面具有巨大潛力。1.2姜黃素1.2.1姜黃素的簡介姜黃素（Curcumin）是一種黃色多酚類化合物，提取自傳統(tǒng)中藥材姜黃（Curcumalonga）的根莖組織。其化學(xué)結(jié)構(gòu)特征為兩個鄰甲氧基苯酚單元通過α,β-不飽和二酮連接橋形成高度共軛的平面結(jié)構(gòu)。這一特殊構(gòu)型使其能夠與多種生物分子（如蛋白質(zhì)、DNA）相互作用，從而表現(xiàn)出顯著的抗炎、抗氧化、抗菌及抑制腫瘤細胞生長的功能ADDINEN.CITEADDINEN.CITE.DATA[27]。然而，姜黃素在應(yīng)用中面臨三大瓶頸：水溶性極低（常溫下約11ng/mL，難以被腸道吸收）、口服生物利用度低（<1%）及體內(nèi)快速代謝（半衰期約0.8小時）ADDINEN.CITEADDINEN.CITE.DATA[28,29]。通過結(jié)構(gòu)修飾（如環(huán)糊精包合、金屬螯合）或納米遞送系統(tǒng)（脂質(zhì)體、聚合物納米粒），可顯著提升其穩(wěn)定性和靶向性。實驗證明，經(jīng)改良的姜黃素制劑生物利用度可提升至天然姜黃素的10倍以上ADDINEN.CITE<EndNote><Cite><Author>Yallapu</Author><Year>2013</Year><RecNum>240</RecNum><DisplayText><styleface="superscript">[29]</style></DisplayText><record><rec-number>240</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1746117222">240</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yallapu,M.M.</author><author>Jaggi,M.</author><author>Chauhan,S.C.</author></authors></contributors><auth-address>CancerBiologyResearchCenter,SanfordResearch/UniversityofSouthDakota,SiouxFalls,SD57104,USA.</auth-address><titles><title>Curcuminnanomedicine:aroadtocancertherapeutics</title><secondary-title>CurrPharmDes</secondary-title></titles><periodical><full-title>CurrPharmDes</full-title></periodical><pages>1994-2010</pages><volume>19</volume><number>11</number><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents,Phytogenic/administration&</keyword><keyword>dosage/chemistry/pharmacokinetics/*therapeuticuse</keyword><keyword>BiologicalAvailability</keyword><keyword>Chemistry,Pharmaceutical</keyword><keyword>Curcumin/administration&dosage/analogs&</keyword><keyword>derivatives/chemistry/pharmacokinetics/*therapeuticuse</keyword><keyword>*DrugCarriers</keyword><keyword>Humans</keyword><keyword>*Nanomedicine</keyword><keyword>Neoplasms/*drugtherapy/metabolism/pathology</keyword><keyword>Technology,Pharmaceutical/*methods</keyword></keywords><dates><year>2013</year></dates><isbn>1381-6128(Print) 1381-6128</isbn><accession-num>23116309</accession-num><urls></urls><custom1>CONFLICTOFINTERESTTheauthorsconfirmthatthisarticlecontenthasnoconflictsofinterest.</custom1><custom2>PMC3640558</custom2><custom6>NIHMS439708</custom6><electronic-resource-num>10.2174/138161213805289219</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[29]。1.2.2姜黃素在IBD中的作用姜黃素通過干預(yù)IBD的核心信號網(wǎng)絡(luò)發(fā)揮治療作用。抗炎機制方面，姜黃素可直接抑制IκB激酶（IKK）的磷酸化，阻斷NF-κB通路向細胞核的轉(zhuǎn)位，同時下調(diào)MAPK通路中ERK和JNK蛋白的活化，從而顯著減少TNF-α、IL-1β和IL-6等促炎因子的轉(zhuǎn)錄與分泌ADDINEN.CITE<EndNote><Cite><Author>Jurenka</Author><Year>2009</Year><RecNum>241</RecNum><DisplayText><styleface="superscript">[30]</style></DisplayText><record><rec-number>241</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1746117753">241</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Jurenka,J.S.</author></authors></contributors><auth-address>ThorneResearch,Inc.jjurenka@</auth-address><titles><title>Anti-inflammatorypropertiesofcurcumin,amajorconstituentofCurcumalonga:areviewofpreclinicalandclinicalresearch</title><secondary-title>AlternMedRev</secondary-title></titles><periodical><full-title>AlternMedRev</full-title></periodical><pages>141-53</pages><volume>14</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Anti-InflammatoryAgents/*pharmacology/*therapeuticuse</keyword><keyword>AntineoplasticAgents/pharmacology/therapeuticuse</keyword><keyword>AutoimmuneDiseases/drugtherapy</keyword><keyword>CardiovascularDiseases/drugtherapy</keyword><keyword>ClinicalTrialsasTopic</keyword><keyword>Curcuma</keyword><keyword>Humans</keyword><keyword>Inflammation/drugtherapy</keyword><keyword>MetabolicDiseases/drugtherapy</keyword><keyword>Neoplasms/drugtherapy</keyword><keyword>NeurodegenerativeDiseases/drugtherapy</keyword><keyword>PlantExtracts/*pharmacology/*therapeuticuse</keyword></keywords><dates><year>2009</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1089-5159(Print) 1089-5159</isbn><accession-num>19594223</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[30]。此外，姜黃素促進Nrf2與抗氧化反應(yīng)元件（ARE）結(jié)合，驅(qū)動超氧化物歧化酶（SOD）、過氧化氫酶（CAT）和谷胱甘肽過氧化物酶（GPx）的基因表達，將腸道內(nèi)ROS水平降低40%～60%ADDINEN.CITEADDINEN.CITE.DATA[31]。此外，姜黃素可上調(diào)腸上皮細胞中Occludin和ZO-1等緊密連接蛋白的合成，修復(fù)因炎癥損傷而增大的細胞間隙，有效阻止細菌內(nèi)毒素從腸腔向血液的易位ADDINEN.CITEADDINEN.CITE.DATA[32]。姜黃素對IBD的治療作用還體現(xiàn)在腸道菌群重塑上。其通過抑制革蘭氏陰性致病菌（如腸桿菌科）脂多糖（LPS）的生物合成，減少TLR4/MyD88通路介導(dǎo)的免疫激活，同時促進乳酸菌和雙歧桿菌等益生菌的增殖，從而改善腸道菌群多樣性并恢復(fù)微生態(tài)平衡ADDINEN.CITEADDINEN.CITE.DATA[33]。1.3氧化鈰1.3.1氧化鈰的簡介氧化鈰（CeO2）作為一種稀土氧化物，因其獨特的螢石型立方晶系結(jié)構(gòu)及可調(diào)控的表面特性，在納米材料領(lǐng)域展現(xiàn)出重要應(yīng)用價值。其晶體結(jié)構(gòu)由Ce??離子構(gòu)成的八面體骨架與O2?離子共同構(gòu)成，通過水熱法、溶膠-凝膠法等合成策略可精準調(diào)控材料形貌，獲得納米顆粒、納米線、納米管及納米片等不同維度結(jié)構(gòu)ADDINEN.CITE<EndNote><Cite><Author>Ma</Author><Year>2022</Year><RecNum>162</RecNum><DisplayText><styleface="superscript">[34]</style></DisplayText><record><rec-number>162</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1716803446">162</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ma,Y.</author><author>Tian,Z.</author><author>Zhai,W.</author><author>Qu,Y.</author></authors></contributors><auth-address>KeyLaboratoryofSpecialFunctionalandSmartPolymerMaterialsofMinistryofIndustryandInformationTechnology,SchoolofChemistryandChemicalEngineering,NorthwesternPolytechnicalUniversity,Xi'an,710072China.GRID:grid.440588.5.ISNI:0000000103071240</auth-address><titles><title>InsightsoncatalyticmechanismofCeO(2)asmultiplenanozymes</title><secondary-title>NanoRes</secondary-title></titles><periodical><full-title>NanoRes</full-title></periodical><pages>10328-10342</pages><volume>15</volume><number>12</number><edition>20220711</edition><keywords><keyword>ceria</keyword><keyword>heterogeneouscatalysis</keyword><keyword>nanozyme</keyword><keyword>oxygenvacancy</keyword></keywords><dates><year>2022</year></dates><isbn>1998-0124(Print) 1998-0000</isbn><accession-num>35845145</accession-num><urls></urls><custom2>PMC9274632</custom2><electronic-resource-num>10.1007/s12274-022-4666-y</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[34]。值得注意的是，納米CeO?的物理化學(xué)性質(zhì)（如比表面積、氧空位濃度）和催化活性高度依賴于其形貌特征，這為功能化設(shè)計提供了關(guān)鍵切入點。CeO2納米材料的生物醫(yī)學(xué)應(yīng)用潛力主要歸因于其類酶抗氧化活性，可模擬過氧化氫酶（CAT）、過氧化物酶（POD）及超氧化物歧化酶（SOD）的催化功能ADDINEN.CITE<EndNote><Cite><Author>李鋒</Author><Year>2022</Year><RecNum>52</RecNum><DisplayText><styleface="superscript">[35]</style></DisplayText><record><rec-number>52</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1712477047">52</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>李鋒</author><author>李雪</author><author>柏娜</author><author>李健</author></authors></contributors><auth-address>青島大學(xué)口腔醫(yī)學(xué)院;青島大學(xué)附屬醫(yī)院口腔修復(fù)科;</auth-address><titles><title>氧化鈰納米顆粒促成骨分化及其對相關(guān)致病菌抗菌作用的研究進展</title><secondary-title>吉林大學(xué)學(xué)報(醫(yī)學(xué)版)</secondary-title></titles><periodical><full-title>吉林大學(xué)學(xué)報(醫(yī)學(xué)版)</full-title></periodical><pages>1348-1353</pages><volume>48</volume><number>05</number><keywords><keyword>氧化鈰納米顆粒</keyword><keyword>氧化還原反應(yīng)</keyword><keyword>促成骨分化作用</keyword><keyword>抗菌作用</keyword></keywords><dates><year>2022</year></dates><isbn>1671-587X</isbn><urls><related-urls><url>/doi/10.13481/j.1671-587X.20220531</url></related-urls></urls><electronic-resource-num>10.13481/j.1671-587X.20220531</electronic-resource-num><remote-database-provider>Cnki</remote-database-provider></record></Cite></EndNote>[35]。這種多酶仿生特性使其能夠高效清除自由基及活性氧（ROS），從而有效保護生物系統(tǒng)免受氧化損傷。其抗氧化機制的核心在于Ce3?/Ce??氧化還原對的動態(tài)循環(huán)：Ce??的半充滿4f軌道（電子構(gòu)型[Xe]4f?）賦予其強氧化性，而Ce3?的未成對4f電子（[Xe]4f1）則使其具備還原能力。這種獨特的電子結(jié)構(gòu)使CeO?在反應(yīng)中可逆地發(fā)生Ce???Ce3?的價態(tài)轉(zhuǎn)換，不僅驅(qū)動了ROS的歧化與分解，還為其催化氧化反應(yīng)（如CO氧化）、還原反應(yīng)（如NOx轉(zhuǎn)化）及裂解反應(yīng)（如水分解）提供了電子傳遞通道ADDINEN.CITE<EndNote><Cite><Author>Chen</Author><Year>2022</Year><RecNum>154</RecNum><DisplayText><styleface="superscript">[36]</style></DisplayText><record><rec-number>154</rec-number><foreign-keys><keyapp="EN"db-id="atzs09sav2att3edf5tv9vryrftrsvdx02s5"timestamp="1716799468">154</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Chen,Xiwen</author><author>Cheng,Chaoqun</author><author>Cheng,Yuan</author><author>Zhao,Sheng</author><author>Wei,Hui</author></authors></contributors><auth-address>CollEngn&ApplSci,DeptBiomedEngn,NanjingNatlLabMicrostruct,JiangsuKeyLabArtificialFunctMat,Nanjing210023,PeoplesRChina NanjingUniv,Chem&BiomedInnovatCtrChemBIC,SchChem&ChemEngn,StateKeyLabAnalytChemLifeSci,Nanjing210023,PeoplesRChina NanjingUniv,Chem&BiomedInnovatCtrChemBIC,SchChem&ChemEngn,StateKeyLabCoordinatChem,Nanjing210023,PeoplesRChina</auth-address><titles><title>CeO2@montmorilloniteNanozymeforCrohn'sDiseaseTherapy</title><secondary-title>CHEMICALJOURNALOFCHINESEUNIVERSITIES-CHINESE</secondary-title></titles><periodical><full-title>CHEMICALJOURNALOFCHINESEUNIVERSITIES-CHINESE</full-title></periodical><volume>43</volume><number>12</number><section>CollEngn&ApplSci<