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1、雷帕霉素抑制大鼠移植肝膽管上皮細(xì)胞增殖作用畢業(yè)：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“2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>20
2、0IU/L、ALP>160IU/L、TB>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
3、%)明顯降低，膽管周圍肌纖維母細(xì)胞分布較少。結(jié)論冷保存蒼俟嘧⒅苯鈾鶘爍臥啵誘導(dǎo)膽管上皮細(xì)胞增殖及肌纖維母細(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】ObjectiveToinvestigatetheinhibitiveeffectofrapamycinonproliferationofbiliaryepithelialcellsandactivationofperibiliaryfibroblas
4、tafterratlivertransplantation.MethodsAfterratlivertransplantationmodeladebasedon“tethod,SDratslydividedintocoldpreservation(CP)for1hourgroup(CP1hourgroup),CP12hoursgroup,rapamycingroup(CP12hoursgrouptreatedycin)andcontrolgroup.Alanineaminotransferase(ALT),total
5、bilirubin(TB)andalkalinephosphatase(ALP)inedatdays1,3,7and14afterlivertransplantation.Immunohistochemicalmethodyofibroblasts,andsurvivalrateofeachgroupALTol/L,ol/L).Atdifferenttimepoints,proliferationratesofbiliaryepithelialcellsinedmarkedlysurroundingthebiledu
6、ctsatdays7and14ycingroup,proliferationrateofbiliaryepithelialcellsarkeddecreaseofmyofibroblastsaccumulationsurroundingthebileductinparisonagetotheliverandsubsequentlyinduceproliferationofbiliaryepithelialcellsandaccumulationofperibiliaryfibroblast.Theproliferat
7、ionofbiliaryepithelialcellsandactivationofperibiliaryfibroblastcanbeinhibitedbyrapamycinthatmayexertprotectiveeffectontheliver.【Keyycin;Livertransplantation;Coldpreservation;Reperfusion;Biliaryepithelialcells;Proliferation肝移植術(shù)后常見的膽道并發(fā)癥為非吻合口狹窄，占所有膽道并發(fā)癥的20%［1］，而冷
8、保存蒼俟嘧⒍緣ü蓯韉鬧苯鈾鶘聳譴死嗖⒎⒅⒅匾的因素。作為肝移植過程中不可避免的病理生理過程，冷保存蒼俟嘧⒅苯鈾鶘說ü萇掀は赴，誘導(dǎo)正常情況下處于細(xì)胞周期靜止?fàn)顟B(tài)的膽管上皮細(xì)胞發(fā)生增殖。這種對(duì)損傷做出的修復(fù)過程極有可能并發(fā)其他膽道疾?。?］。因此研究影響膽管上皮細(xì)胞增殖的因素對(duì)于臨床防治膽道疾病具有重要意義。本研究是在大鼠原位肝移植模型基礎(chǔ)上，探
