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1、雷帕霉素抑制大鼠移植肝膽管上皮細(xì)胞增殖作用的研究作者：陳莉萍戴睿武郭毅斌王曙光董家鴻'【摘要】目的探討雷帕霉素對(duì)大鼠移植肝膽管上皮細(xì)胞增殖及其周圍成纖維細(xì)胞活化的抑制作用。方法“二袖套法”建立大鼠原位肝移植模型，并隨機(jī)分為供肝冷保存1h組、12h組、雷帕霉素組(冷保存12h組術(shù)后給予雷帕霉素)、對(duì)照組。分別于術(shù)后1、3、7、14d檢測血清ALT、TB、ALP，免疫組化法檢測各組膽管上皮細(xì)胞增殖率及肌纖維母細(xì)胞分布，并統(tǒng)計(jì)各組生存率。結(jié)果冷保存12h組術(shù)后生存率明顯低于冷保存1h組(P=0.0174)，血清ALT>200IU/L、ALP>160IU/L、TB&
2、gt;3.6μmol/L，持續(xù)高于冷保存1h組(ALT<160IU/L、ALP<200IU/L、TB<3.6μmol/L)，各時(shí)相點(diǎn)膽管上皮細(xì)胞增殖率(7%,27.8%,23.1%,17.8%)顯著高于冷保存1h組(2%,6%,2.6%,2.3%)和對(duì)照組(1.3%)。冷保存12h組術(shù)后7、14d可見膽管周圍較多肌纖維母細(xì)胞聚集；雷帕霉素組術(shù)后2周生存率與冷保存12h組接近(P=0.89)，膽管上皮細(xì)胞增殖率(5.9%,15.8%,13.6%,11.4%)明顯降低，膽管周圍肌纖維母細(xì)胞分布較少。結(jié)論冷保存再灌注直接損傷肝臟，誘導(dǎo)膽管上皮細(xì)胞增殖及肌纖
3、維母細(xì)胞聚集，雷帕霉素明顯抑制膽管上皮細(xì)胞增殖及肌纖維母細(xì)胞活化并對(duì)移植肝具有保護(hù)作用?！娟P(guān)鍵詞】雷帕霉素；肝移植；冷保存；再灌注；膽管上皮細(xì)胞；增殖【Abstract】ObjectiveToinvestigatetheinhibitiveeffectofrapamycinonproliferationofbiliaryepithelialcellsandactivationofperibiliaryfibroblastafterratlivertransplantation.MethodsAfterratlivertransplantationmodelwasmade
4、basedon“twocuff”method,SDratswererandomlydividedintocoldpreservation(CP)for1hourgroup(CP1hourgroup),CP12hoursgroup,rapamycingroup(CP12hoursgrouptreatedwithrapamycin)andcontrolgroup.Alanineaminotransferase(ALT),totalbilirubin(TB)andalkalinephosphatase(ALP)weredeterminedatdays1,3,7and14aft
5、erlivertransplantation.Immunohistochemicalmethodwasusedtodetectproliferationrateofbiliaryepithelialcellsanddistributionofmyofibroblasts,andsurvivalrateofeachgroupwasalsoanalyzed.ResultsThesurvivalrateinCP12hoursgroupwassignificantlylowerthanthatinCP1hourgroup(P=0.0174).InCP12hoursgroup,s
6、erumALTwas>200IU/L,ALP>160IU/LandTB>3.6μmol/L,whichweresignificantlyhigherthanthoseinCP1hourgrouprespectively(ALT<160IU/L,ALP<200IU/L,TB<3.6μmol/L).Atdifferenttimepoints,proliferationratesofbiliaryepithelialcellswere7%,27.8%,23.1%and17.8%inCP12hoursgroup,butwere2%,6%,2.
7、6%and2.3%6inCP1hourgroupand1.3%incontrolgroup,withstatisticaldifference.Myofibroblastsweredeterminedmarkedlysurroundingthebileductsatdays7and14whilesurvivalratesignificantlydecreasedinCP12hoursgroup.Inrapamycingroup,proliferationrateofbiliaryepithelialcellswassignificantl
