维生素A缺乏联合 CCl4 诱导制备稳定的小鼠慢性肝纤维化模型
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A stable mouse model of chronic liver fibrosis induced by vitamin A deficiency and intraperitoneal CCl4 injection
YANGTingting，ZHAOLi
Departmentoticiute'sialoiceityalcalsee ChildHealthandisordersinistryofducationKeyLaboratoryfildDeelopmentandDsordersChoningKeybatoryf Structural irthDefectandReconstruction，Chongqing4Ooo14，China
Abstract：ObjectiveToprepareastablemousemodelofchronicliverfibrosisinducedbydietaryvitaminA（VA）deficiency combined with CCl4 injections.MethodsAtotalof126Balb/cmice wererandomized into3groupsfor feeding withanormal VA diet or a VA-deficient diet containing 500 or 200IU/kg VA. After 4 weeks of feeding，half of the mice in each group were given intraperitoneal injectionsof 5%CCl4（10mL/kg， twicea week） for8weeks.Serumretinol，ALT/ASTand liver indexof the micewereexaminedivertisuepathologieswereobservedwithHEandMassonsainingandliverfibrosisoeand oxidativestresslevelwereevaluated.ResultsFourweeksofVA-deficientfeeding，especiallat20oIU/kg，significantly lowered serum retinol level of the mice. CCl4 injections for 8 weeksobviously increased liver index and ALT/ASTand caused obviousliverfibrosisinalltemice，butliverpathologiesweremoresevereinthe2VA-deficientgroups;severelivercrosis with inflammatory cell infiltration was observed in 200IU/kg VA group， where 2 mice died.After discontinuation of CCl4′ the mice withnormaldietaryVAshowedgradualrecoveryofthliverindex，ALT/AST，ivercordstructureandliverfibosis;the micewithVAdeficiencyowever，sowednosignificantimprovementsintheseparameters，andthemicewith 200IU/kg VA stillhadseriousabdomialdesion，falselobulsandmasiveiflmmatorycellinfiltrationitharosisstageoof3. The oxidative damage index 8-OHdG was significantly higher in 500IU/kg VA group than in normal VA group after CCl4 modeling.ConclusionFeedingwithdietcontaining 500IU/kg VAfor4weeksand 10mL/kg CCl4 injections for8weekscan resultinstablemoderatetosevereliverfibrosisinmicewithoutspontaneousreversalat8weeksofdrugwithdrawal.
Keywords：vitaminAdeficiency; CCl4′ chronic liver fibrosis;animal models
肝纤维化是慢性肝脏损伤相关的肝脏瘢痕修复反应，是多种慢性肝病进展至肝硬化的中间过程，由多种致病因子诱发肝内结缔组织异常增生，导致肝内细胞外基质（ECM）过度沉积引起2。（剩余14326字）
