雷帕霉素抑制大鼠移植肝胆管上皮细胞增殖作用的研究.doc

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1、雷帕霉素抑制大鼠移植肝胆管上皮细胞增殖作用的研究作者：陈莉萍戴睿武郭毅斌王曙光董家鸿'【摘要】目的探讨雷帕霉素对大鼠移植肝胆管上皮细胞增殖及其周围成纤维细胞活化的抑制作用。方法“二袖套法”建立大鼠原位肝移植模型，并随机分为供肝冷保存1h组、12h组、雷帕霉素组(冷保存12h组术后给予雷帕霉素)、对照组。分别于术后1、3、7、14d检测血清ALT、TB、ALP，免疫组化法检测各组胆管上皮细胞增殖率及肌纤维母细胞分布，并统计各组生存率。结果冷保存12h组术后生存率明显低于冷保存1h组(P=0.0174)，血清ALT>200IU/L、ALP>160IU/L、TB&

2、gt;3.6μmol/L，持续高于冷保存1h组(ALT<160IU/L、ALP<200IU/L、TB<3.6μmol/L)，各时相点胆管上皮细胞增殖率(7%,27.8%,23.1%,17.8%)显著高于冷保存1h组(2%,6%,2.6%,2.3%)和对照组(1.3%)。冷保存12h组术后7、14d可见胆管周围较多肌纤维母细胞聚集；雷帕霉素组术后2周生存率与冷保存12h组接近(P=0.89)，胆管上皮细胞增殖率(5.9%,15.8%,13.6%,11.4%)明显降低，胆管周围肌纤维母细胞分布较少。结论冷保存再灌注直接损伤肝脏，诱导胆管上皮细胞增殖及肌纤

3、维母细胞聚集，雷帕霉素明显抑制胆管上皮细胞增殖及肌纤维母细胞活化并对移植肝具有保护作用。【关键词】雷帕霉素；肝移植；冷保存；再灌注；胆管上皮细胞；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