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3D evaluation model for drug hepatotoxicity testing on HepG2 cells and its application in drug safety evaluation

3D HepG2细胞药物肝毒性评价模型的建立及其在药物安全性评价中的应用



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3DevaluationmodelfordrughepatotoxicitytestingonHepG2celsandits
applicationindrugsafetyevaluation
LIDandan1,2,TANGXianglin2,TANHongling2,LIANGQiande2,WANGYuguang2,
MAZengchun2,XIAOChengrong2,GAOYue1,2
(1GuangxiMedicalUniversity,Nanning530021,China;
2InstituteofRadiationMedicine,AcademyofMilitaryMedicalSciences,Beijing100850,China)
[Abstract] 3Dinvitrotoxicitytestingmodelwasdevelopedbymagneticlevitationmethodforcultureofthehumanhepatomacelline
HepG2andappliedtoevaluatethedrughepatotoxicityAfterformationofstable3DstructureforHepG2cels,theirglycogenstorage
capacityunder2Dand3Dcultureconditionsweredetectedbyimmunohistochemistrytechnology,andthemRNAexpressionlevelsof
phaseⅠ andⅡ drugmetabolismenzymes,drugtransporters,nuclearreceptorsandliverspecificmarkeralbumin(ALB)werecom
paredbetween2Dand3DcultureconditionsbyusingRTPCRmethodImmunohistochemistryresultsshowedthatHepG2celshad
abundantglycogenstoragecapacityunder3Dcultureconditions,whichwassimilartohumanlivertissuesThemRNAexpressionlevels
ofmajordrugmetabolismenzymes,drugtransporters,nuclearreceptorsandALBinHepG2celsunder3Dcultureconditionswereup
regulatedascomparedwith2DcultureconditionsFordrughepatotoxicityevaluation,thetypicalhepatotoxicdrugacetaminophen
·3131·
2016
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Vol41,No.7 April,2016
(APAP),andmostreporteddrugsPolygonummultiflorumThunb(ChinesenameHeshouwu)andPsoraleaecorylifoliaL(Chinese
nameBuguzhi)wereselectedforsingledoseandrepeateddose(7d)exposureIntherepeateddoseexposuretest,3DHepG2cels
showedhighersensitivityThisestablished3DHepG2celsmodelwithmagneticlevitation3Dculturetechniqueswasmoreclosetothe
humanlivertissuesbothinmorphologyandfunctions,soitwasabeter3Dhepatotoxicityevaluationmodel
[Keywords] 3Dculture;hepatotoxicity;evaluationmodel
doi:10.4268/cjcmm20160725
  
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