中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2012年
8期
1503-1505
,共3页
王光锁%王正%武延格%杨林%孙学峰%钱有辉%林少霖
王光鎖%王正%武延格%楊林%孫學峰%錢有輝%林少霖
왕광쇄%왕정%무연격%양림%손학봉%전유휘%림소림
肺移植%闭塞性细支气管炎%免疫耐受
肺移植%閉塞性細支氣管炎%免疫耐受
폐이식%폐새성세지기관염%면역내수
Lung transplantation%Obliterative bronchiolitis%Immunological tolerance
目的 探讨供体特异性输注(DST)联合共刺激阻断(DST/抗CD154)诱导肺移植后闭塞性细支气管炎(OB)免疫耐受机制.方法 建立小鼠DST/抗CD154方案诱导的免疫耐受模型术后15、25、100 d取出移植气道检测形态学改变,利用CSME-80鼠cDNA芯片检测15d耐受组和同种异体移植组移植物内基因表达差异,分析差异有统计学意义的基因表达与排斥和耐受之间的关系.选择部分差异表达基因行实时荧光定量逆转录-聚合酶链反应( RT-qPCR),鉴定验证基因芯片的可靠性.结果 免疫耐受组OB前期存在大量显著表达差异基因,Rapl信号通路、CD40/CD40L相关及其他T细胞表面分子相关基因、细胞周期、细胞生长等促进纤维增殖的部分基因显著下调表达.部分促炎因子同同种异体移植组一样上调表达.结论 Rap1信号通路、CD40/CD40L相关及其他T细胞表面分子相关基因、细胞周期、细胞生长等促进纤维增殖下调表达的部分基因等可能与肺移植慢性排斥反应耐受相关.
目的 探討供體特異性輸註(DST)聯閤共刺激阻斷(DST/抗CD154)誘導肺移植後閉塞性細支氣管炎(OB)免疫耐受機製.方法 建立小鼠DST/抗CD154方案誘導的免疫耐受模型術後15、25、100 d取齣移植氣道檢測形態學改變,利用CSME-80鼠cDNA芯片檢測15d耐受組和同種異體移植組移植物內基因錶達差異,分析差異有統計學意義的基因錶達與排斥和耐受之間的關繫.選擇部分差異錶達基因行實時熒光定量逆轉錄-聚閤酶鏈反應( RT-qPCR),鑒定驗證基因芯片的可靠性.結果 免疫耐受組OB前期存在大量顯著錶達差異基因,Rapl信號通路、CD40/CD40L相關及其他T細胞錶麵分子相關基因、細胞週期、細胞生長等促進纖維增殖的部分基因顯著下調錶達.部分促炎因子同同種異體移植組一樣上調錶達.結論 Rap1信號通路、CD40/CD40L相關及其他T細胞錶麵分子相關基因、細胞週期、細胞生長等促進纖維增殖下調錶達的部分基因等可能與肺移植慢性排斥反應耐受相關.
목적 탐토공체특이성수주(DST)연합공자격조단(DST/항CD154)유도폐이식후폐새성세지기관염(OB)면역내수궤제.방법 건립소서DST/항CD154방안유도적면역내수모형술후15、25、100 d취출이식기도검측형태학개변,이용CSME-80서cDNA심편검측15d내수조화동충이체이식조이식물내기인표체차이,분석차이유통계학의의적기인표체여배척화내수지간적관계.선택부분차이표체기인행실시형광정량역전록-취합매련반응( RT-qPCR),감정험증기인심편적가고성.결과 면역내수조OB전기존재대량현저표체차이기인,Rapl신호통로、CD40/CD40L상관급기타T세포표면분자상관기인、세포주기、세포생장등촉진섬유증식적부분기인현저하조표체.부분촉염인자동동충이체이식조일양상조표체.결론 Rap1신호통로、CD40/CD40L상관급기타T세포표면분자상관기인、세포주기、세포생장등촉진섬유증식하조표체적부분기인등가능여폐이식만성배척반응내수상관.
Objective To define the molecular mechanism of obliterative bronchiolitis (OB) following heterotopic tracheal transplantation during the early stages of tolerance induction by donor specific transfusion and anti-CD154.Methods Tolerance induction was achieved in tracheal allografts from BALB/C to C57BL/6 mice by donor specific transfusion of splenocytes intravenously and intraperitoneal injection of anti-CD154 mAbs.The differential gene expression was detected in tolerant murine heterotopic tracheal allografts by means of gene microarrays.Differential expression of selected genes was confirmed bv real-time fluorescent quantitative reverse transcription ( RT-qPCR).Results Comparative analysis between DST/anti-CD154 protocol-induced tolerant and rejected grafts revealed many genes were specifically downregulated in the tolerant allografts,including RAP1 pathway,CD40/CD40L concerned T cell surface molecules and many profibrotic genes,which were upregulated in the rejected allografts.In the tolerant allografts there was also marked expression of a number of genes for proinflammatory factors.Conclusion These results suggest a vital role for RAP1 pathway,CD40/CD40L concerned T cell surface molecules and many profibrotic genes in inducing airway transplant tolerance in this model.