血红素加氧酶1延长异种心脏移植存活的机制研究

探讨血红素加氧酶1(heme oxygenase-1,HO-1)在器官移植中抗急性血管排斥反应的作用。通过建立豚鼠到SD大鼠异位心脏移植模型,用血红素(hemin)分别诱导供者和受者,上调HO-1基因表达;用眼镜蛇毒因子、环孢素A抑制超急性排斥反应;观测供者心脏存活时间,并分别检测心脏组织HO-1表达、受者血清异种抗体IgM的变化及异种抗体IgM和C3在血管内膜的沉积;采用TUNEL方法检测心脏组织细胞凋亡;RT-PCR方法测定组织CD40L mRNA表达水平。结果显示:上调HO-1表达能明显延长心脏移植存活时间,抑制异种抗体IgM表达和在血管内膜的沉积,减少心肌细胞的凋亡并且抑制CD40L mRNA的表达。该结论表明HO-1通过介导CD40-CD40L共刺激途径抑制大鼠异种心脏移植后急性血管排斥反应,延长心脏移植存活时间。

Heme oxygenase 1 prolongs the survival of acute cardiac xenograft rejection

In order to investigate the effect of heme oxygenase 1(HO-1) to prolong the survival of acute cardiac xenograft rejection,the guinea pig to rat cardiac allograft model was established,and the model animals were pre-treated with hemin before transplantation to up-regulate the expression of the HO-1 gene,with the concomitant use of cobra venom factor(CVF) and cyclosporin A(CsA) to prevent the occurrence of the hyperacute rejection.The expression of HO-1 in cardiac tissues and the levels of the serum xeno-reactive antibody IgM and the deposits of the xeno-reactive antibody IgM and C3 in vascular tunica intima in the experimental animals were detected respectively.In addition,apoptosis of the cardiac tissue cells and the level of CD40L mRNA were determined with TUNEL and RT-PCR assay respectively. The experimental results showed that the over-expression of HO-1 could prolong the survival of the acute cardiac allograft rejection and reduce the occurrence of serum xeno-reactive antibody IgM as well as the xeno-reactive antibody IgM and C3 deposits in vascular tunica intima.Apoptosis of myocardial cells could bereduced and the expression of CD40L mRNA could be suppressed with the expression of HO-1 in cardiac cells in the period of acute vascular rejction.It is evident the expression of heme oxygenase 1 suppresses the acute vascular rejection and prolongs the survival of the acute xenograft rejection in guinea pig to rat cardiac xenograft model through blockage of the CD40-CD40L costimulatory pathway.