摘要
目的 :研究 NF-κB活性抑制对再灌注早期供肝损伤的保护作用。方法 :改良 Kam ada法建立同种大鼠原位肝脏移植模型 ,实验分对照组和二硫代氨基甲酸吡咯烷 (PDTC)组 ,对照组供肝于 4℃乳酸林格液中保存 6 h,PDTC组供肝于乳酸林格冷保存液中加入 0 .1mol/L PDTC,于再灌注早期分析测定供肝组织中 NF-κB的结合活性 (EMSA法 )、TNF-α和 ICAM- 1的 m R-NA转录水平 (RT- PCR)以及 AL T和 L DH的活性变化。结果 :供肝组织的 NF-κB在移植后再灌注早期明显激活 ;再灌注 1h,PDTC组的 NF-κB活性较对照组显著降低 ,但 6 h后两组 NF-κB活性未见明显差异。再灌注早期 TNF-α和 ICAM- 1m RNA转录水平上调以及 AL T和 L DH活性升高 ,但 PDTC组明显低于对照组 (P<0 .0 5 )。结论 :供肝组织中 NF- κB的活性抑制可显著降低再灌注早期供肝组织中炎症介质的转录表达 ,并有效改善供肝的再灌注损伤。针对 NF- κB的靶向治疗可能是供肝保护的一条新途径。
Objective:To investigate the protective effects of nuclear factor κB inhibition on liver graft reperfusion injury during transplantation.Methods:Orthotopic liver transplantation using modified cuff technique was established in rats,animals were divided according to the grafts cold storaged in 4℃ Ringer's lactated solution with(PDTC group)or without 0.1 mol/L PDTC(control group)for 6 h.During the early stage of reperfusion,DNA binding activities of NF κB in liver grafts were analyzed by EMSA(electrophoretic mobility shift assay),mRNA level of TNF α and ICAM 1 by RT PCR,and activities of ALT and LDH were also detected.Results:NF κB in liver grafts was activated at early stage of reperfusion during transplantation; PDTC treated liver displayed lower activation of NF κB 1 h after reperfusion,whereas no difference was shown between 2 groups 6 h after reperfusion.Up regulation of TNF α and ICAM 1 transcription,high level of ALT and LDH activities were observed in both groups during reperfusion,whereas the transcriptional up regulation and the activities of ALT and LDH in PDTC group were reduced compared with those of control group( P <0.05).Conclusion:Inhibition of NF κB in liver graft down regulates the transcription of inflammatory media and attenuates liver graft function at the early stage of reperfusion during transplantation.Therapies targeting NF κB may be a promising method to protect the liver graft injury.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2002年第7期741-744,共4页
Academic Journal of Second Military Medical University
基金
国家自然科学基金资助项目 (C3 0 0 0 0 15 8)
