短鏈脂肪酸與糖尿病認(rèn)知功能障礙

糖尿病認(rèn)知功能障礙(diabeticcognitiveimpairment,DCI)作為糖尿病的神經(jīng)hort-chainfattyacids,S認(rèn)知功能障礙及DCI人群中的變化特征，并梳理了SCFAs在DCI中的作用機(jī)制，種類、不同劑量的SCFAs在DCI中的效果及潛在機(jī)制，從而為防治“共病模式”國(guó)際糖尿病聯(lián)盟數(shù)據(jù)顯示，2021年全球20~79歲人群中的糖尿病患者人數(shù)為5.37億，預(yù)計(jì)到2030年和2045年將分別增加到6.43億和7.83億[1]。一項(xiàng)全國(guó)性發(fā)生輕度認(rèn)知功能障礙(mildcognitiveimpatient,MCI)和癡呆的風(fēng)險(xiǎn)分別是正常人群的1.44倍和2.14倍[5-6]。一項(xiàng)Meta分析顯示，全球DCI的總體患病近年來(lái)，短鏈脂肪酸(short-chainfatty能之間的聯(lián)系逐漸成為研究熱點(diǎn)。SCFAs是腸道菌群利用膳食纖維發(fā)酵的代謝產(chǎn)乙酸是外周循環(huán)中最豐富的SCFAs,含量最高，通過(guò)中樞穩(wěn)態(tài)機(jī)制穿過(guò)血腦屏障一、文獻(xiàn)檢索作者在中國(guó)知網(wǎng)、萬(wàn)方、PubMed、Embase及WebofScience等數(shù)據(jù)庫(kù)進(jìn)行中英文文獻(xiàn)檢索，檢索時(shí)間從數(shù)據(jù)庫(kù)建庫(kù)至2024年3月。中文檢索詞包括“2干擾腦內(nèi)Aβ的降解，增加其神經(jīng)毒性并促進(jìn)認(rèn)知功能障礙的發(fā)生與發(fā)展[14]。因而針對(duì)性地補(bǔ)充SCFAs或促進(jìn)SCFAs的產(chǎn)生有望成為管理T2DM的一種潛在方2.SCFAs在認(rèn)知功能障礙患者中的變化特征：Wu等[21]對(duì)22名MCI患者、27名阿爾茨海默病(Alzheimer'sdisease,AD)患者及28名健康對(duì)照者糞便的SI和健康對(duì)照組中的鑒別效果最好。然而，另一項(xiàng)研通過(guò)對(duì)認(rèn)知功能障礙人群進(jìn)行了為期12年的隨訪，最終發(fā)現(xiàn)血清中丙酸水平與是DCI發(fā)病的關(guān)鍵機(jī)制[33]。與正常對(duì)照小鼠相比，db/db小鼠海馬組織中的A要作用[34]。Fernando等[35]將AD模型小鼠(5xFAD)隨機(jī)分為對(duì)照飲食組和丁加乙酸和丁酸的飲食則通過(guò)減少小鼠大腦皮質(zhì)的Aβ斑塊延緩了其認(rèn)知能力的研究通過(guò)對(duì)AD轉(zhuǎn)基因小鼠(APP/PS1)進(jìn)行9個(gè)月的混合SCFAs(乙酸、丙酸和丁3.炎性反應(yīng)：以T2DM為代表的代謝性疾病的共同特征是慢性炎性反應(yīng)的激i等[42]通過(guò)對(duì)高果糖喂養(yǎng)的C57BL/6小鼠進(jìn)行持續(xù)8周的混合SCFAs(乙酸、丙酸和丁酸)干預(yù)，結(jié)果發(fā)現(xiàn)SCFAs干預(yù)增加小鼠海馬齒狀回(de中的新生神經(jīng)元(DCX+),這表明SCF發(fā)現(xiàn)混合SCFAs(乙酸：丙酸：丁酸=3:1:1)干預(yù)能夠顯著減輕認(rèn)知功能障礙5的磷酸化水平。另一項(xiàng)研究對(duì)T2DM模型小鼠(KK-Ay)進(jìn)行了為期8周的丁酸干小鼠中被激活，而丁酸有效降低了NLRP3的蛋白水平。Bayazid等[49]將4周齡病低血糖相關(guān)的認(rèn)知功能障礙與線粒體自噬受損有關(guān)，表現(xiàn)為PIN一步采用丙酸、丁酸和丙戊酸分別對(duì)糖尿病小鼠進(jìn)行干預(yù)，結(jié)果顯示在給藥14改善db/db小鼠的認(rèn)知功能障礙[30]?？蒣1]SunH,Saeediionalandcountry-leveldiabetespreojectionsfor2045[J].DiabetesResClinPract,20210.1016/j.diabres.2021.109119.[2]LiY,TengD,ShiX,etal.Prevalenceofdiabetesssociation:nationalcrosssectionalstudy[J].BMJ,2020,I:10.1136/bmj.m997.2022,38(6):453-464.DOI:10.3760/311282-20220.EndocrinologyBranchofChineseMedicalAssociation,ChineseAdultType2DiabetesBloodPressureTreatmentTargetResearchWorkingGroitiveimpairmentiseJournalofEndocrinologyandMetabolism,2022,38(6):453-464.DOI:10.3760/311282-2MedicalUniversit,2023,40(3):262-267.DOI:10.7683/xxyxyxb.esAging,2023,45(2):161-172.DOI:10.1177/01640275221084282.[6]JiaL,DuY,ChuL,etal.Prevalence,riskfactors,andmanagement5(12):e661-e671.DOI:10.1016/S2468-2667(20)30185-7.[7]YouY,LiuZ,ChenY,etal.Theprevalenceofmildcognitiveimpairmentintype2diabetesmellituspatients:asystematita-analysis[J].ActaDiabetol,2021,7/s00592-020-01648-9.87,28(10):1221-1227.DOI:10.1136/gut.28.10.1221.研究進(jìn)展[J].國(guó)際內(nèi)分泌代謝雜志，2022,42(3):211-214.DOI:10.3760/121383-20210105-01012.ChenRH,PengYD.Associationsofintestinalfloraanditsdysfunction[J].IntJEndocrinolMetab,2022,42(3):211-214.D10.3760/121383-ncer,andbeyond[J].TrendsCellBiol,2019,29(9):695-703.DOI:10.10[11]DalileB,VanOudenhoveL,VervlietB,etal.TherolnfattyacidsoenterolHepatol,2019,16(8):461-478.DOI:10.1038/s41575-019[12]ShiehJC,HuangPT,LinYF.Alzheimer'sdiseaselinsignalingasthebr1,2020,57(4):1966-1977.DOI:10.1007/s1203resistanceintype2diabetnundrums[J].NatRevNeurol,2018,14(3):168-181.DOI:10.1038/nrneurol.2017.185.[14]LiX,SongD,LengSX.Linkbetsdisease:fromepidervAging,2015,10:549-560.DOI:10.2147/CIA.S74042.002076.LiuSL,LuYH,LiMZ.Researchainducedbytype2diabetes[J].JournalofChongqingty,2019,44(4):404-410.DOI:10.13406/ki.cyxb.002076.ordersandAlzheimer'sdisease[J].Biology(Basel),2023,12(7):10DOI:10.3390/biology12071019.cma.j.issn.1674-6554.2018.08.001.FengXQ,ZhaChronicbraindiseaseandcognitiveimpairment:researchprogressanDOI:10.3760/cma.j.issn.1674-6554.2018.08.001.[18]SuceveanuAI,StoianAP,ParepaI,etal.Gutmicrobiotapatternsi37358/RC.18.8.6512.ydietaryfibersalleviatetype2diabetes[J].Science,2018,359(0):1151-1156.DOI:10.1126/science.aao5774.gthegutmicrobiome,shor[J].NatGenet,2019,51(4):600[21]WuL,HanY,ZhengZ,etal.AlteredgutmicrobiamnesticmildcognitiveimpairmentandAlzheimer'sdisease:signahost-microbeinterplay[J].Nutrients,2021,13(1):228.DOI:10.3390/nu13010228.acidlevelsinpatientswithmildcognitiveimpairments[J].CNSsciTher,2023,29(11):3657-3666.DOI:10.1111/cns.14252.ofcognitiveimpairmentinAlzheimer'sdisease[J].IntJMolSci,2022,24(1):707.DOI:10.3390/ijms24010707.[24]DuY,LiX,AnY,etal.AssociationofinfattyacidsandtNutr,2022,9:930626.DOI:10.3389/fnut.2022.930626.[25]NeufferJ,González-Domínguetionofthegut-braina[J].Nutrients,2022,14(21):4688.DOI:10.3390/nu1421iomarkersintheprogressionoftypveimpairmentpatients:across-sectionalstudy[J].InterdisciplinaryNursingResearch,2023,2(1):19-26.DOI:10.1097/NR9.000000000000ptorFFAR2[J].Diabetes,2012,61(2):364-371.DOI:10.2337/dbl1-1019.[28]ChristiansenCB,GabeM,SvendsenB,etal.Theimpaatcolon[J].AmJPhysiolGastrointestLive3-G65.DOI:10.1152/ajpgi.00346.2017.provementinobesityandneurobehavitCellInfectMicrobiol,2023,13:1178399.DOI:10.3389/fcimb.2023.Commun,2020,11(1):855.DOI:10.1038/s41467-020-14676-4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