摘要
目的以基因工程干细胞治疗的方式来改善缺血-再灌注状况,使移植肝脏更好地耐受缺血-再灌注,以减少移植术后的并发症,延长移植器官存活期。方法利用已建立的Wistar大鼠冷缺血原位肝移植(OLT)模型,术中经受体大鼠门静脉输入IL-13基因修饰的或未修饰的肝卵圆细胞(HOC)即转染组和未转染组,分别于术后1、3、7及14d检测受体大鼠肝脏功能变化、组织学变化、胆管上皮细胞(BEC)的增殖情况、α-平滑肌肌动蛋白(α-SMA)的表达、肝组织中HO-1 mRNA的表达,并观察移植大鼠术后的存活情况。结果转入IL-13基因的HOC对冷保存损伤的肝脏有一定的保护作用;术后7d,肝移植组和未转染组的α-SMA表达较转染组明显(P<0.05);术后3d,未转染组和转染组的BEC增殖指数明显低于肝移植组(P<0.05)。转染组术后各时相点的HO-1 mRNA表达水平均明显高于相应时相点的其他各组的水平(P<0.05);移植术中经门静脉输入HOC对缺血性胆管损伤所诱导的BEC增殖有一定的抑制作用,对BEC具有一定的保护作用;肝移植组生存率明显低于假手术组和转染组(P<0.05)。结论IL-13的持续表达能促进术后移植肝内HO-1 mRNA的表达,这有利于对供肝的保护,有利于受体大鼠术后肝功能的恢复。促进HO-1 mRNA的表达是IL-13对BEC的具有保护作用的机理之一。
Objective Biliary epithelial cell （BEC） proliferated actively induced by ischemia-type biliary lesion （ITBL）,which played an important role in the development of biliary complication after orthortopic liver transplantation （OLT）. The aims of this study is to provide novel method to protect the liver endured cold preservation and reperfusion injury （CPRI） and reduce posttransplant biliary complication,and explore its possible mechanism. Methods Based on constructed OLT models for studying ITBL,the hepatic oval cell （HOC） or the IL-13 gene-modified HOC to the portal vein of the recipient 〔OLT＋HOC group and OLT＋IL-13· HOC group〕 were transfused,then the pathology change,the liver function and the expressions of the α-smooth muscle actin （α-SMA） and Heme oxygenase-1 （HO-1） mRNA of the transplanted liver of CPRI were observed,the proliferation of BEC and survival rate of the recipients were also observed. Results The BEC injury was showed in grafts with prolonged ischemia time,characterized by induction of BEC proliferation,liver function injury and cholestasis sign reflecting the increase of serum ALT,AST and TBIL. The OLT＋IL-13·HOC group had better results than OLT and OLT＋HOC group,which indicated the OLT＋IL-13·HOC group had low level of expression α-SMA （after operation 7 d,P0.05） and proliferation of BEC （after operation 3 d,P0.05）. The expressions of HO-1 mRNA were higher in OLT＋IL-13·HOC group than in other groups. The survival rate of OLT group was lower than that of the OLT＋IL-13·HOC group and sham operation group （P0.05）. Conclusion High expression level of IL-13 in recipient rats could promote the expression of HO-1 mRNA in transplant liver,and profit to protection donor liver,and recover of the liver function after liver transplantation. It perhaps is the mechanism of protective effect of IL-13 on graft that stimulate the expression of HO-1 mRNA significantly.
出处
《中国普外基础与临床杂志》
CAS
2010年第2期135-141,共7页
Chinese Journal of Bases and Clinics In General Surgery
基金
中国博士后科学基金一等资助课题(项目编号:20060400199)
关键词
慢病毒
白介素-13
肝干细胞
肝移植
缺血性胆管损伤
血氧合酶-1
Lentivirus
Interleukin-13
Hepatic stem cell
Liver transplantation
Ischemia-type biliary lesion
Heme oxygenase-1
