CHOP在急性缺血性肾损伤炎症反应中的作用与机制

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1、第三军医大学硕士学位论文转染PEGFP．CHOP的HKC细胞在荧光显微镜下可检测到绿色荧光信号。转染PEGFP．CHOP的HKC细胞CHOP蛋白、II水NA表达显著高于对照组。转染CHOPsiRNA的细胞CHOP蛋白、mRNA表达显著低于对照组。PEGFP．CHOP转染的HKC细胞与100uIIlolH202孵育12h后，培养上清LDH水平升高，细胞存活率降低；细胞培养上清中IL．1B、IL．6和IL．8水平显著高于PEGFP．N1+H202组和HKC+H202组。转染CHOPsiRNA的HKC细胞与100u】nolH202孵育12h后，LDH漏出

2、量降低，细胞存活率升高；细胞培养上清中IL一1B、IL．6和IL．8水平显著低于对照siRNA+H202组和HKC+H202组。．三、结论I瓜和H202可上调肾组织和培养的肾小管上皮细胞CHOP表达，同时增强炎症细胞因子的产生和释放。过表达CHOP加重H202诱导HKC表达炎症细胞因子和细胞损伤；抑制CHOP表达可减轻H202诱导的炎症反应和细胞损伤。提示内质网应激上调CHOP表达可能在急性缺血性肾损伤中具有重要作用。关键词：缺血再灌注；肾小管上皮细胞；CHOP；内质网应激；炎症9第三军医大学硕士学位论文TheroleandmechanismofC

3、HoPininnammatory—J■●1J●■●reSD0nSeatterⅪdneVaCUtelSCnemlClnlUryAbstractAcutekidneyinju巧(AKI)isassociatedwithahi曲degreeofmorbidityandmortality．InmaIlysurgicalandmedicalsettings，ischemicAⅪplaysadominaIltroleinmepathogenesisofAKI．AKIisalsoaIlinflammatorydisease，butthemechanismshow

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5、rpoxiaorenergydepriVationcouldactiVateaseriesofpannerproteins，tranlscriptionfactorsalldproteinkinases，andmeninitiateendoplasmicreticulumstress(ERS)．Studieshavesho、ⅣnthatappropriateERScouldmaintaincellhomeostasisalldpreservecen劬ction；howeVer，prolongedall讹rexcessERSleadst0celliI

6、】：ju巧锄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铲owtllarrestorDNAdamageinduciblegene153，GADDl53)isanimportantpro-apoptoticmoleculedistributedintheendoplasmicreticulum．RecentstudyfoundmatactiVatio

8、nofCHOPcouldcauseinn撇matoryresponse，forexample，CHOPknockoutco