中华器官移植杂志
中華器官移植雜誌
중화기관이식잡지
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
2012年
8期
462-465
,共4页
袁清%洪善娟%蔡明%王毅%张雷%曾力%朱有华
袁清%洪善娟%蔡明%王毅%張雷%曾力%硃有華
원청%홍선연%채명%왕의%장뢰%증력%주유화
小鼠%肾移植%一氧化碳%树突细胞%移植物排斥
小鼠%腎移植%一氧化碳%樹突細胞%移植物排斥
소서%신이식%일양화탄%수돌세포%이식물배척
Mice%Kidney transplantation%Carbon monoxide%Dendritic cells%Graft rejection
目的 研究水溶性一氧化碳释放分子3 (CORM-3)减轻小鼠肾移植后排斥反应的作用及机制.方法 以C57BL/6J小鼠为供鼠,Balb/c小鼠为受鼠,采用随机数字表法将供、受鼠分为2组,制备小鼠肾移植模型.CORM-3组受鼠接受经CORM-3预处理的供肾,iCORM组受鼠接受经无CO活性的iCORM预处理的供肾.术后检测各组受鼠的血清肌酐(SCr)水平,观察各组移植肾组织的病理改变,记录各组移植肾存活时间.以C.FVB-Tg (Itgax-DTR/GFP) 57Lan/J小鼠为供鼠,Balb/c小鼠为受鼠,肾移植后24 h通过流式细胞仪检测移植肾内供鼠rDC的活化情况.结果 术后iCORM组和CORM-3组间移植肾中位存活时间分别为40.5和70 d(P<0.05);术后两组受鼠的SCr水平均进行性升高,但CORM-3组受鼠的SCr水平始终保持在较低的水平(P<0.05或P<0.01);与正常小鼠肾组织相比,术后第4周iCORM组受鼠的移植肾间质出现弥漫性单个核细胞浸润,中度肾小管炎症,以及部分肾小球硬化;CORM-3组移植肾组织单个核细胞浸润较iCORM组明显减轻,肾小球与肾小管形态基本正常.移植后24 h,iCORM组和CORM-3组移植肾内供鼠rDC表面均高表达CD80和CD86,表明rDC处于活化状态,而CORM-3组rDC表面CD80和CD86的表达较iCORM组明显减少(P<0.05).结论 CORM-3可显著减轻同种肾移植小鼠的排斥反应,改善移植肾功能,其机制可能是CORM-3抑制了移植后供鼠rDC的活化.
目的 研究水溶性一氧化碳釋放分子3 (CORM-3)減輕小鼠腎移植後排斥反應的作用及機製.方法 以C57BL/6J小鼠為供鼠,Balb/c小鼠為受鼠,採用隨機數字錶法將供、受鼠分為2組,製備小鼠腎移植模型.CORM-3組受鼠接受經CORM-3預處理的供腎,iCORM組受鼠接受經無CO活性的iCORM預處理的供腎.術後檢測各組受鼠的血清肌酐(SCr)水平,觀察各組移植腎組織的病理改變,記錄各組移植腎存活時間.以C.FVB-Tg (Itgax-DTR/GFP) 57Lan/J小鼠為供鼠,Balb/c小鼠為受鼠,腎移植後24 h通過流式細胞儀檢測移植腎內供鼠rDC的活化情況.結果 術後iCORM組和CORM-3組間移植腎中位存活時間分彆為40.5和70 d(P<0.05);術後兩組受鼠的SCr水平均進行性升高,但CORM-3組受鼠的SCr水平始終保持在較低的水平(P<0.05或P<0.01);與正常小鼠腎組織相比,術後第4週iCORM組受鼠的移植腎間質齣現瀰漫性單箇覈細胞浸潤,中度腎小管炎癥,以及部分腎小毬硬化;CORM-3組移植腎組織單箇覈細胞浸潤較iCORM組明顯減輕,腎小毬與腎小管形態基本正常.移植後24 h,iCORM組和CORM-3組移植腎內供鼠rDC錶麵均高錶達CD80和CD86,錶明rDC處于活化狀態,而CORM-3組rDC錶麵CD80和CD86的錶達較iCORM組明顯減少(P<0.05).結論 CORM-3可顯著減輕同種腎移植小鼠的排斥反應,改善移植腎功能,其機製可能是CORM-3抑製瞭移植後供鼠rDC的活化.
목적 연구수용성일양화탄석방분자3 (CORM-3)감경소서신이식후배척반응적작용급궤제.방법 이C57BL/6J소서위공서,Balb/c소서위수서,채용수궤수자표법장공、수서분위2조,제비소서신이식모형.CORM-3조수서접수경CORM-3예처리적공신,iCORM조수서접수경무CO활성적iCORM예처리적공신.술후검측각조수서적혈청기항(SCr)수평,관찰각조이식신조직적병리개변,기록각조이식신존활시간.이C.FVB-Tg (Itgax-DTR/GFP) 57Lan/J소서위공서,Balb/c소서위수서,신이식후24 h통과류식세포의검측이식신내공서rDC적활화정황.결과 술후iCORM조화CORM-3조간이식신중위존활시간분별위40.5화70 d(P<0.05);술후량조수서적SCr수평균진행성승고,단CORM-3조수서적SCr수평시종보지재교저적수평(P<0.05혹P<0.01);여정상소서신조직상비,술후제4주iCORM조수서적이식신간질출현미만성단개핵세포침윤,중도신소관염증,이급부분신소구경화;CORM-3조이식신조직단개핵세포침윤교iCORM조명현감경,신소구여신소관형태기본정상.이식후24 h,iCORM조화CORM-3조이식신내공서rDC표면균고표체CD80화CD86,표명rDC처우활화상태,이CORM-3조rDC표면CD80화CD86적표체교iCORM조명현감소(P<0.05).결론 CORM-3가현저감경동충신이식소서적배척반응,개선이식신공능,기궤제가능시CORM-3억제료이식후공서rDC적활화.
Objective To investigate the effect and underling mechanism of water-soluble CO-releasing molecules (CORM-3) on the alleviation of allograft rejection after mouse kidney transplantation.Methods A mice kidney transplantation model was established using C.FVB-Tg (Itgax-DTR/GFP)57Lan/J or C57BL/6J (H-2Kb) mice as donors,and Balb/c (H-2Kd) mice as recipients.After donor nephrectomy,kidney was preserved in UW solution which contained CORM-3 or iCORM (inactive CO-releasing molecules) for 24 h in 4℃.Recipient survival after removal of both na? ve kidneys,serum creatinine as well as graft histology was observed.In the C.FVB-Tg(ItgaxDTR/GFP) 57Lan/J donors,rDCs were acquired in vitro and selected by magnetic cell sorting (MACS) after graft nephrectomy.The expression of activation markers,CD80 and CD86,on rDC was assessed by using flow cytometry.Results The graft medium survival time was 40.5 days in the iCORM group and 70 days in the CORM-3 group respectively (P<0.05).CORM-3 preserved the graft function as shown by significantly lower serum creatinine (P<0.05; or P<0.01) and alleviated graft pathology injury.Diffuse infiltration of mononuclear cells in the interstitial tissues,moderate tubulitis and partial glomerular sclerosis were found in the iCORM graft kidney,while the CORM-3 graft kidney displayed almost normal histology.Meanwhile,CORM-3 suppressed the expression of CD80 and CD86 in donor-derived rDC.Conclusion CORM-3 can alleviate allograft rejection,prolong the graft survival,and improve kidney function in mouse kidney transplantation,probably via inhibiting rDC activation.