You Position: Home > Paper
Administration of NF-κB decoy oligodeoxynucleotides palliates ischemia-reperfusion injury of rat liver graft
( views:236, downloads:20 )
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 10
- DOI:
- 10.3760/cma.j.issn.0254-1785.2006.10.003
- Key Word:
- 枯否细胞;核因子κB;肝移植
Abstract： 目的 探讨抑制枯否(Kupffer)细胞核因子κB(Nuclear factor-kappaB,NF κB)活性对减轻大鼠移植肝缺血/再灌注损伤(IRI)的作用和机制.方法 建立大鼠肝移植缺血/再灌注损伤模型.实验分正常对照组、缺血/再灌注组和圈套寡核苷酸组,每组均为8只大鼠.圈套寡核苷酸组于移植术前2 d经供者尾静脉注入120μg脂质体包裹的NF-cB圈套寡核苷酸.移植再灌注后2h,取各组受者移植肝分离枯否细胞.凝胶迁移变动分析法(EMSA)检测枯否细胞NF-κB蛋白结合活性,逆转录聚合酶链法(RT-PCR)观察枯否细胞肿瘤坏死冈子a(TNF-α)和白细胞介素6(IL-6)mRNA的表达,同时观察肝组织病理及肝功能变化.结果 缺血/再灌注组移植肝再灌注后2h,枯否细胞NFKB活性及TNF-α、II-6 mRNA表达量较对照组明显升高(P＜0.01).光镜下肝细胞大量变性、坏死,伴有肝血窦明显淤血,血清丙氨酸转氨酶(ALT)和胆红素总量(TBIL)较对照组明显升高(P＜0.01).相反,圈套寡核苷酸组枯否细胞NF-κB活性及细胞因子mRNA表达与缺血/再灌注组相比明显下降(P＜0.01),移植肝未见明显病理组织学改变,肝功能明显改善.结论 NF-κB圈套寡核苷酸能高效抑制枯否细胞NF-κB活性,并抑制其下游有害细胞因子的产生,从而减轻缺血/再灌注损伤对移植肝的打击和损害.
- [1]Finke JH,Molto L,Derweesh I,etc.Degradation of NF-kappaB in T cells by gangliosides expressed on renal cell carcinomas.[J].2004,172(6).
- [2]M, Ozaki,S, Haga,K, Irani,etc.Overexpression of redox factor-1 protects against postischemic liver injury by reducing oxidative stress and NF-kappa B activity.[J].2002,34.
- [3]Zettl UK,Kluter A,Neeck G,etc.Transcription factors in autoimmune diseases.[J].2004,10(23).
- [4]Sato M,Satomi S,Masamume A,etc.Kupffer cells play an important role in the cytokine production and activation of nuclear factors of liver grafts from non-heart-beating donors.[J].2002,15(8).
- [5].Improved Two-Cuff Technique for Orthotopic Liver Transplantation in Rat[J].2004,(1).
- [6]Ohkohchi N,Masamune A,Oikawa K,etc.Elimination of Kupffer cells suppresses activation of nuclear factor kappa B and production of cytokines and eicosanoids in non-heart-beating donors.[J].2001,33(1).
- [7]Hunter CA,Mason NJ,Artis D.New lessons from old pathogens: what parasitic infections have taught us about the role of nuclear factor-kappaB in the regulation of immunity.[J].2004,201(0).