白介素4下调thp-1巨噬细胞源性泡沫细胞abca1的表达及其胆固醇流出word论文.docxVIP

Interleukin-4 Down-regulates LXR-dependent Expressionof ABCA1 inTHP-1Macrophage-Derived FoamCellsAbstractObjective:Thestudywas to investigate theeffects ofIL-4 onABCA1 expressionandcholesteroleffluxinhumanTHP-1macrophage-derivedfoamcells.Whetherthe liver Xreceptoralpha (theLXRα)is involved in its regulation.Methods:THP-1cellsbyphorbolester-inducedadherent,addingoxLDLinducedto becomefoamcells.，addingwithdifferentconcentrationsanddifferenttimesofIL-4 as well as small moleculesinterferingRNA(siRNA) treatmentfactors,SpecificmRNAwasquantifiedbyreal-timePCR,proteinexpressionbyWesternblotting.In tissuemorphologystaininglipidaccumulationwasdeterminebytheoilredO.Liquid scintillationcountingandhighperformanceliquidchromatographyassayswereused to test cellularcholesterol effluxand cholesterol content.Results:IL-4significantlydecreasedtheexpressionofABCA1 andcholesteroleffluxintheTHP-1macrophage-derivedfoamcells.LiverXreceptor(LXRα)Playan important role inIL-4 downregulatingofABCA1,so theLXRαsiRNAcan also reverse the effect ofIL-4.Conclusions:IL-4 decreased ABCA1 expression and inhibited cholesterolefflux,whichwasmediatedbyaccompanyingLXRα inhibition.IL-4wastime-and concentration-dependentinhibitionofABCA1expressionandcholesteroleffluxlin THP-1macrophage-derivedfoamcells.Whichmaybeinvolvedinthe LXRα playingregulation ofABCA1 expression in the cells andicholesterolefflux.Keywords:ATP-bindingcassettetransporterA1,ATP-bindingcassettetransporterA1,2Interleukin-4, liverXreceptor,AtherosclerosisPostgraduate:Chun-zhiTan (majorin medicine) DirectedbyProfessor: ChaokeTang, JieWu3引言大量文献研究表明，血浆高密度脂蛋白（HDL)水平的降低是心血管疾病发生的独立危险因素，相反随着HDL的升高，心血管的发生率大大降低，HDL干预实验（HIT）和流行病学研究表明，HDL每增加1%，冠心病（CHD）的危险性就降低 2-3%[1-3】。其主要原因是其在胆固醇逆向转运（RCT)过程中发挥重要作用。RCT 指的是血浆脂蛋白将外周组织(包括动脉壁)游离胆固醇转运至肝脏，并通过肝脏排泄的过程，它包括两个步骤:(l)清除外周细胞中游离胆固醇;(2)转运HDL中的游离胆固醇于肝脏[4]。在动脉粥样硬化（AS)斑块中，泡沫细胞的主要来源之一是巨噬细胞，所以巨噬细胞内胆固醇的流出障碍对动脉粥样硬化的进展有着重要作用[5]。胆固醇流出是RCT的第一步，也是其关键一步。三磷酸腺苷结合盒转运体A1（ABCA1）在胆固醇逆向转运途径第一步中发挥着重要的作用，ABCA1主要促进胆固醇和磷脂从巨噬细胞