Effect of intercellular adhesion molecule-1 antisense oligodeoxynucleotide on xenografts

Objective To investigate the inhibitory effect of intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ICAM-1-ASO) on the rejection of cardiac xenograft as well as the expression of ICAM-1 in the xenograft.Methods BALB/C mice and Lewis rats served as donors and recipients respectively. The mouse-to-rat heterotopic heart transplantation model was established. The hearts of normal BALB/C mice were harvested as control group. The xengrafts were divided into three groups: ddH2O group, control oligodeoxynucleotide group and ICAM-1-ASO group (n=10 in each group). Each donor was injected intravenously with ddH2O, control oligodeoxynucleotide or ICAM-1-ASO 6 h before operation respectively. At 48th h after transplantation, 5 xenografts in each group were collected for histopathological examination. The expression of ICAM-1 protein and mRNA in cardiac xenografts was detected by immunohistochemical method and semiquantitative reverse transcriptase polymerase reaction method. The mean survival time (MST) in each xenograft group was recorded in terms of the other 5 transplanted grafts by palpation per 12 h.Results Faint ICAM-1 expression was observed in the control group. In ddH2O group and control oligodeoxynucleotide group, capillary endothelial cells and myocytes of the grafts strongly expressed ICAM-1 and the relative density values (ICAM-1/β-actin) were also significantly higher with extensive hyperemia, edema, hemorrhage and inflammatory cells infiltrated in both groups than those in the control group. Comparatively, in the ICAM-1-ASO group, fainter ICAM-1 expression was observed and the relative density value (ICAM-1/β-actin) was also significantly lower with pathological improvement compared with those in ddH2O group and control oligodeoxynucleotide group. The MST in ICAM-1-ASO was (66.4±2.61) h, which was significantly prolonged as compared with ddH2O group and control oligodeoxynucleotide group.Conclusion ICAM-1-ASO can sequence-dependently inhibit the ICAM-1 expression of xenografts, suppress xenograft rejection and prolong the survival time of xenografts.