慢性胰腺炎发病的遗传学基础及防治分析-genetic basis and prevention of chronic pancreatitis.docxVIP

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慢性胰腺炎发病的遗传学基础及防治分析-genetic basis and prevention of chronic pancreatitis.docx

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慢性胰腺炎发病的遗传学基础及防治分析-genetic basis and prevention of chronic pancreatitis

第二军医大学博士学位论文theexpressionofplasmaglutathioneperoxidase(GPx3)inearly-onsetICPpatientswasmarkedlylowerthanthatinlate-onsetones,andthelevelsofplasma8-OHdGandMDAintheearly-onsetpatientgroupweresignificantlyincreasedascomparedtothoseofthelate-onsetpatientsandhealthycontrols.ThemicroRNAchipanalysisshowedthatthelevelofhsa-miR-453waslowerinlate-onsetpatientswhencomparedtotheearly-onsetgroup.Invitroexperimentsconfirmedthathsa-miR-453caneffectivelyinhibitluciferaseactivityofpMIR-reporter-GPx3.Here,usinggenomics,proteomicsandmicroRNAchipanalysis,wedemonstratedthatthec.194+2TCvariantofSPINK1wasnottheonlydeterminantfactorforearly-onsetICPbutratherthatGPx3playedakeyroleinthisetiopathogenesisofearly-onsetdiseasebydiminishingantioxidantactivity.Moreover,throughinvitroexperiments,wefoundthatup-regμlatedhsa-miR-453ledtoloweredexpressionofGPx3.Thisfindingprovidesmethodsandnewideasforfurtherstudyoftheearly-onsetmechanismsofICP.Becausetheetiologyofchronicpancreatitisiscomplicated,theexactmechanismofdiseasehasnotbeenfμllyclarified,thetreatmentofchronicpancreatitisisstillaproblem.Endoscopictranspapillarypancreaticductdrainageistheprocedureofchoicefordilatedpancreaticductinpatientswithchronicpancreatitis.However,itmaybeunsuccessfμlin5-10%ofcases.RecentlytheuseofEus-guideddrainageofpancreaticducthasbeenreported,butitisnotclearwhetheritisfeasibleforthistechniquetofindmorewidespreaduseasanalternativetofailedERCP.WehereindescribeourexperiencewithacaseofchronicpancreatitiscomplicatedbyWhippleprocedurewithdialedpancreaticductsuccessfμllytreatedbyEus-guidedpancreaticductdrainage.Thispaperisdividedintofourparts:Partone:ThegeneticanalysisofthechronicpancreatitisofHanpopμlationinmainlandChina;Parttwo:MicroRNA-453down-regμlatesPlasmaGlutathioneperoxidaseinearly-onsetidiopathicchronicpancreatitispatients:apotentialdiseasemechanism?Partthree:Endoscopicμltrasound-guidedtransgastricpancreaticductdrainageafterWhipplesurgeryinapatientwithchronicpancreatitis;Partfour:Reviewoftheetiology，treatmentofchronicpa