糖脂毒性诱导胰岛β细胞炎症因子过表达的研究.pdfVIP

糖脂毒性诱导胰岛β细胞炎症因子过表达的研究

胡朝恩;钟大鹏;艾智华

【摘要】ObjectiveThisstudywasdesignedtoinvestigatetheeffectsof

highglucoseandhighfatenvi-ronmentonthefunctionofisletβ-celland

expressionofTollreceptor3(TLR3),tumornecrosisfactor-α(TNF-

α),interleukin-1β(IL-1β),interleukin6(IL-6),C-reactive

protein(CRP),complementC3andcomple-mentC4.MethodsThecultured

isletβcellline(NIT-1)wasstimulatedbyhighglucoseandhighfat,andthe

cellproliferationwasdetectedbyCCK-8method,TLR3mRNAexpression

wasdetectedbyrealtimefluores-cencequantitativepolymerasechain

reaction(RT-PCR)andthelevelsofTNF-α,IL-1β,IL-6,CRP,comple-mentC3

andcomplementC4incellculturesupernatantweredetectedbyenzyme-

linkedimmunosorbentassay(ELISA).ResultsTheproliferationofisletbeta

cellswasinhibitedafterhighglucoseandhighfatstimula-tion,however,the

expressionofTLR3mRNA,TNF-α,IL-1β,IL-6,CRP,complementC3and

complementC4wereincreasesignificantly.Theextentofisletβcell

damageandover-expressionofinflammatorycytokinesweresignificantly

higherinhighglucoseandlipid(GZ)groupthanthoseinhigh

glucose(G)grouporhighfat(Z)group(P＜0.05).ConclusionHighglucose

andhighlipidmayproducealargenumberofinflammato-ryfactorsand

immunefactorsthroughtheactivationofTLR3signalingpathway,inhibit

theproliferationofis-letbetacellsandleadtoisletbetacell

dysfunction,andthesynergisticeffectofsugarandfatissignificantly

greaterthanthatofindividualglucoseandlipidtoxicity.%目的了解高糖、高

脂环境对胰岛β细胞功能和Toll受体3(TLR3)、肿瘤坏死因子-α(TNF-α)、白细胞

介素-1β(IL-1β)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、补体C3及补体C4表

达的影响.方法培养小鼠胰岛β细胞株(NIT-1)经高糖高脂刺激后,应用CCK-8试剂

盒检测细胞增殖情况,采用实时荧光定量聚合酶链反应(RT-PCR)检测TLR3mRNA

的表达,采用酶联免疫吸附试验(ELISA)检测细胞培养上清液中TNF-α、IL-1β、

IL-6、CRP、补体C3及补体C4的表达.结果高糖高脂刺激后,胰岛β细胞增殖被

抑制,TLR3mRNA、TNF-α、IL-1β、IL-6、CRP、补体C3及补体C4的表达

明显增加;并且高糖高脂(GZ)组胰岛β细胞损伤和炎症因子过表达程度明显高