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1、第三軍醫(yī)大學碩士學位論文轉染PEGFP．CHOP的HKC細胞在熒光顯微鏡下可檢測到綠色熒光信號。轉染PEGFP．CHOP的HKC細胞CHOP蛋白、II水NA表達顯著高于對照組。轉染CHOPsiRNA的細胞CHOP蛋白、mRNA表達顯著低于對照組。PEGFP．CHOP轉染的HKC細胞與100uIIlolH202孵育12h后，培養(yǎng)上清LDH水平升高，細胞存活率降低；細胞培養(yǎng)上清中IL．1B、IL．6和IL．8水平顯著高于PEGFP．N1+H202組和HKC+H202組。轉染CHOPsiRNA的HKC細胞與100u】nolH202孵育12h后，LDH漏出
2、量降低，細胞存活率升高；細胞培養(yǎng)上清中IL一1B、IL．6和IL．8水平顯著低于對照siRNA+H202組和HKC+H202組。．三、結論I瓜和H202可上調腎組織和培養(yǎng)的腎小管上皮細胞CHOP表達，同時增強炎癥細胞因子的產生和釋放。過表達CHOP加重H202誘導HKC表達炎癥細胞因子和細胞損傷；抑制CHOP表達可減輕H202誘導的炎癥反應和細胞損傷。提示內質網應激上調CHOP表達可能在急性缺血性腎損傷中具有重要作用。關鍵詞：缺血再灌注；腎小管上皮細胞；CHOP；內質網應激；炎癥9第三軍醫(yī)大學碩士學位論文TheroleandmechanismofC
3、HoPininnammatory—J■●1J●■●reSD0nSeatterⅪdneVaCUtelSCnemlClnlUryAbstractAcutekidneyinju巧(AKI)isassociatedwithahi曲degreeofmorbidityandmortality．InmaIlysurgicalandmedicalsettings，ischemicAⅪplaysadominaIltroleinmepathogenesisofAKI．AKIisalsoaIlinflammatorydisease，butthemechanismshow
4、inflammator)rresponseisinitiatedaRerkidneyischemia-reper向sionhaVenotbeenmllyunderstood．Endoplasmicreticulumisthela唱estcellularo昭anelleresponsibleforproteinsyntllesis，assemblyandmodification，andplaysaIlimporrtantroleinceUsurviValaIldnomalf．unction．IthasbeenproVedthatischemia，h)
5、rpoxiaorenergydepriVationcouldactiVateaseriesofpannerproteins，tranlscriptionfactorsalldproteinkinases，andmeninitiateendoplasmicreticulumstress(ERS)．Studieshavesho、ⅣnthatappropriateERScouldmaintaincellhomeostasisalldpreservecen劬ction；howeVer，prolongedall訛rexcessERSleadst0celliI
6、】：ju巧鋤dcendeath—Endoplasmicreticulummolecularch叩eroneglucose—regulatedprotein78(GI己P78)andoxygen—regulatedprotein150(OI己P150)areconsideredasmarkersofERS．OnerecentstudyshowedthatStrongendopl嬲micretiCul啪stressandrenaltubularepithelialceUapoptosiscouldbeobserved世ertllerenalanerie
7、sclaI】1pedfor1OmimItes．AnotherstudyfoundthatexcessiVeERScouldinducenotonlycenapoptosisbutalsoinnammatoryresponse．CHOP(alsoknownasa鏟owtllarrestorDNAdamageinduciblegene153，GADDl53)isanimportantpro-apoptoticmoleculedistributedintheendoplasmicreticulum．RecentstudyfoundmatactiVatio
8、nofCHOPcouldcauseinn撇matoryresponse，forexample，CHOPknockoutco
