·508·解放军医学杂志2007年5月第32卷第5期MedJChinPLAVol32No5May2007糖皮质激素对血管内皮炎性损伤的保护机制王兴友陈杭薇钱桂生【摘要】目的探讨糖皮质激素对血管内皮细胞的保护机制。方法以脂多糖(LPS)致伤体外培养的人脐静脉内皮细胞(HIⅣEC)复制内皮细胞炎性损伤模型,观察地塞米松(Dex)作用后其IL-6、可溶性胞间黏附分子1(slCAM-1)分泌及细胞凋亡率的变化,以及糖皮质激素受体拮抗剂RU486对地塞米松作用的影响。结果LPS诱导后HUVEC凋亡率达36.7±3.9,而Dex对此有明显抑制作用,可使凋亡率降至13.2±O.9(P<0.01)。在LPS刺激下,HUVEC分泌IL-6和slCAM-1的量明显增多。Dex可以明显抑制LPS诱导的IL-6、slCAM-1分泌和HUVEC凋亡,且呈一定的浓度依赖性,Dex浓度增加到1Omol/L时,其抑制效应达最大值,继续增加Dex的浓度到10-5tool/L和10tool/L时,并不能再增强其效应。RU486可逆转Dex的作用。结论糖皮质激素可通过糖皮质激素受体途径抑制IL_6与sICAM-1的分泌和细胞凋亡,对血管内皮细胞的炎性损伤起到保护作用。【关键词】糖皮质激素类;内皮,血管;脂多糖类;细胞凋亡【中国图书资料分类号1R364.5StudiesmtheprotectionmechanismofglucocorticoidsagainsttheinflammatoryiIuryofvascularendothelialcellsWangXingyou,ChenHangwei,QianGuisheng.DepartmentofRespiratory,GeneralHospitalofBeringCommand,Beijing100700,China【Al】strad】Objeet~Toexplorethepmtmtionmechanismofglucocorticoids(GC)againsttheinflammatoryinjuryofvascularendothelialcells(vEC).MethodsAninflammatoryinjurymodelofVECwasreproducedbytreatingthehumanumbilicalveinendothelialcells(HUVEC)、Ⅳithlipopolysaccharides(LPS)invitro.Theeffectofdexamethasone(Dex)onapoptosisofH{ECandthereleaseofIL-6andsICAM一10fHIrvECwasobserved,andthentheeffectofRU486(anantagonistforglucocortimidreceptor)onreversingtheeffectofDexwasalsoobserved.ResuRsLPScouldinduceapoptosisofHUVEC,andtheapoptosisratereached36.7±3.9.Ontheotherhand.glucocorticoid(Dex)couldobviouslyinhibittheapoptosisofHUVECinU)s,andtheapoptosisratewasreducedto13.2±0.9.Thedifferencebetweentheapoptosisratebetwenthesetwogroupswasverysignificant(P<0.o1).AlterbeingstimulatedbyLPSHUVECcouldsecreteIL-6andslCAM-1inlargeamount.Glucocorticoid(Dex)couldalsoinhibitthesecretionofIL-6andsICAM—lobviously.BothinhibitionofsecretionofIL-6andsIC1andinhibitionofapoptosisofHUVECweredoes-dependent.TheinhibitioneffectwasmaximalwhentheconcentrationofDexapproached10mol/L。yettheefectscouldnotbeelevatedbyfurtherincreaseofDexconcentrationto10tool/Land10~。tool/LRU486couldreversetheeffectsofDex.ConclusionG1ucocortimidcouldprotectVECfromtheinflammatoryinjurybyinhibitingthesecretionofIL-6andsICAM-1andtheapoptosisofVECthroughthepathwayofglucocorticoidrecepmr.[Key州s】glucocorticoidsendothelium,vascularlipopolysacchafides;apoptosis血管内皮细胞(vascularendothelialcell,Ⅵ1C)是机体一类重要的细胞群体,在血管通透性屏障、免疫防御及炎症反应中起着极其重要的作用_l-。]。Ⅵ1C能够合成并分泌多种活性因子,其中白细胞介素6(interleuldn-6,I6)、可溶性胞间黏附分子1(solubleintercellularadhesionmolecule-1,slCAM-1)较有代表性,而IL-6则被认为是内皮炎症反应的最佳标志分子。宋勇等[研究发现脂多糖(1ipopolysaccharide,LPS)诱导血管内皮细胞凋亡是ARDS发病的病理基础之一,但未观察糖皮质激素(glucocorticoid,GC)的保护作用。本实验以LPS致伤体外培养的人脐静脉内皮细胞(humanumbilicalveinendothelialcell,HUVEC)复制内皮细胞炎性损伤模型,观察糖皮质激素对其IL_6、slCAM-1分泌及细胞凋亡率的影响,以探讨糖皮质激素对血管内皮的保护机制及其在ARDS治疗中的意义。1材料与方法1.1实验材料人脐静脉内皮细胞株来...