短链脂肪酸与糖尿病认知功能障碍

糖尿病认知功能障碍(diabeticcognitiveimpairment,DCI)作为糖尿病的神经hort-chainfattyacids,S认知功能障碍及DCI人群中的变化特征，并梳理了SCFAs在DCI中的作用机制，种类、不同剂量的SCFAs在DCI中的效果及潜在机制，从而为防治“共病模式”国际糖尿病联盟数据显示，2021年全球20~79岁人群中的糖尿病患者人数为5.37亿，预计到2030年和2045年将分别增加到6.43亿和7.83亿[1]。一项全国性发生轻度认知功能障碍(mildcognitiveimpatient,MCI)和痴呆的风险分别是正常人群的1.44倍和2.14倍[5-6]。一项Meta分析显示，全球DCI的总体患病近年来，短链脂肪酸(short-chainfatty能之间的联系逐渐成为研究热点。SCFAs是肠道菌群利用膳食纤维发酵的代谢产乙酸是外周循环中最丰富的SCFAs,含量最高，通过中枢稳态机制穿过血脑屏障一、文献检索作者在中国知网、万方、PubMed、Embase及WebofScience等数据库进行中英文文献检索，检索时间从数据库建库至2024年3月。中文检索词包括“2干扰脑内Aβ的降解，增加其神经毒性并促进认知功能障碍的发生与发展[14]。因而针对性地补充SCFAs或促进SCFAs的产生有望成为管理T2DM的一种潜在方2.SCFAs在认知功能障碍患者中的变化特征：Wu等[21]对22名MCI患者、27名阿尔茨海默病(Alzheimer'sdisease,AD)患者及28名健康对照者粪便的SI和健康对照组中的鉴别效果最好。然而，另一项研通过对认知功能障碍人群进行了为期12年的随访，最终发现血清中丙酸水平与是DCI发病的关键机制[33]。与正常对照小鼠相比，db/db小鼠海马组织中的A要作用[34]。Fernando等[35]将AD模型小鼠(5xFAD)随机分为对照饮食组和丁加乙酸和丁酸的饮食则通过减少小鼠大脑皮质的Aβ斑块延缓了其认知能力的研究通过对AD转基因小鼠(APP/PS1)进行9个月的混合SCFAs(乙酸、丙酸和丁3.炎性反应：以T2DM为代表的代谢性疾病的共同特征是慢性炎性反应的激i等[42]通过对高果糖喂养的C57BL/6小鼠进行持续8周的混合SCFAs(乙酸、丙酸和丁酸)干预，结果发现SCFAs干预增加小鼠海马齿状回(de中的新生神经元(DCX+),这表明SCF发现混合SCFAs(乙酸：丙酸：丁酸=3:1:1)干预能够显著减轻认知功能障碍5的磷酸化水平。另一项研究对T2DM模型小鼠(KK-Ay)进行了为期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]将4周龄病低血糖相关的认知功能障碍与线粒体自噬受损有关，表现为PIN一步采用丙酸、丁酸和丙戊酸分别对糖尿病小鼠进行干预，结果显示在给药14改善db/db小鼠的认知功能障碍[30]。可[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.研究进展[J].国际内分泌代谢杂志，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. thegut-brainneuralmechanismindiabeticmice[J].Microbiome,2029(1):145.DOI:10.1186/s40168-021-01088-9.[32]LiT,YangS,LiuX,etanandimpedesbrainaginginmiceviaregulationofmicrobiotagut-brainaxis[J].JAdvRes,2023,52:119-134.DOI:10.1016/j.jare.rodegenerativediseases[J].Cell,2023,186(4):693-714.DOI:1 j.cell.2022.12.032.[34]ZhengY,WangC,LiuW,etal.UpregulationofNrf2signaliymolecularmechanismofBaicalin'sneuroprotectiveactiabetes-inducedcognitiveimpairment[J].BiomedPharm174:116579.DOI:10.1016/j.biop[35]FernandoW,MartinsIJ,MoriciM,etal.Sodiumbutyratereducesbr[J].JAlzheimersDis,2020,74(1):91-99.DOI:10.3233/JmousemodelofAlzheimer'sdisease[J].JNeurosci,2023,43(37):6460-6475.DOI:10.1523/JNEUROSCI.0724-23.2023.ndmemoryfunctioninmousemodelsciLett,2022,791:136887.DOI:10.1016/j.neulet.2022.136887.dysfunctioninAlzheimer'sdisease[J].MolNeurodegener,2014,9:48.DOI:10.1186/1750-1326-9-48.[39]SunY,ZhangH,ZhangX,etal.Promotiheimer'sdisease[J].RedoxBiol,2023,62:102690.DOI:10.1016/j.reADmice[J].ChemBiolInteract,2021,341:109452.DOI:1i.2021.109452.EPpathway[J].MolPsychiatry,2022,27(8):3396-3409.DOI:10.1ainfattyacids[J].Microbiome,2019,7(1):9nfattyacidsagainstsepsis-associatedencephalopathontImmunol,2021,12:626894.DOI:10.3389/fimmu.2021.626894.[44]ZhangY,ZhaoY,ZhangJ,etal.MechanismsofNLRP3inflammasomeaochemRes,2020,45(11):2560-2572.DOI:10.1007/s11064-020-031[45]ZhangW,XiaoD,MaoQ,etal.Roleofneuroinflammationinneurodegenerationdev67.DOI:10.1038/s41392-023-01486-5.[46]HuangY,XuW,ZhouR.NLRP3inflammh[J].CellMolImmunol,2021,18(9):2114-21241423-021-00740-6.[47fNLRP3inflammasomeregulation[J].JLeukocBiol,2021,109(3):561-571.DOI:10.1002/JLB.3nflammationbyinhibitingNLRP3pathway[J].SciRe