大鼠接受小鼠异种心脏移植后粘附分子ICAM-1的表达

Donor ICAM-1 expression in cardiac xenografts

目的观察大鼠接受小鼠异种心脏移植后延迟性排斥反应(DXR)的病理特征,研究异种心脏移植中粘附分子ICAM-1的表达变化,探讨DXR的发生机制。方法建立Lewis大鼠接受BALB/c小鼠异种心脏移植模型。随机将接受异种心脏移植的大鼠分为5组,每组5只,分别于移植后12、24、36、48 h及移植心停跳时切取移植心;另取5只术前健康雄性BALB/c小鼠心脏作为对照。进行病理学检查、免疫组织化学检测及图象分析定量,研究供者移植心组织中ICAM-1的表达,以及应用半定量逆转录-聚合酶链式(RT-PCR)方法检测移植心组织中ICAM-1 mRNA的表达。结果病理学检查显示移植后12 h,移植心组织中即有间质充血、出血以及少量的炎性细胞浸润;随时间的推移病变不断加重,直至排斥反应的终点呈现典型的DXR。术前对照组心脏组织中ICAM-1表达微弱;异种心脏移植后随着时间的推移,心脏组织中ICAM-1的表达不断增强。半定量RT-PCR结果显示,移植心组织中ICAM-1 mRNA亦随时间的推移进行性增高。结论异种心脏移植后,移植心组织中供者型ICAM-1的表达明显增强,与DXR的发生和发展密切相关;供者型ICAM-1表达增强可较早提示DXR的发生。

Objective To study the pathological characteristics of delayed xenograft rejection and the expression of donor ICAM-1 in mouse-to-rat cardiac xenografts. Methods BALB/c mice and Lewis rats served as donors and recipients respectively. The model of mouse-to-rat heterotopic heart xenotransplantation was established. The cardiac xenografts were harvested at 12 h, 24 h, 36 h, 48 h after transplantation and at the time when no pulsations could be detected in the transplanted heart respectively. The normal BALB/c mouse hearts were harvested as control group. The grafts were col lected to receive pathological and immunohistochemical examinations as well as to detect the level of ICAM-1 mRNA in the xenografts. Quantitive measurement of ICAM-1 expression in the grafts was done by using multimedia pathology imaging analysis system. RT-PCR products of xenografts were separated by agrose gels and the densities of the bands were determined by density scanning. Results The pathologic examination of xenografts showed hyperemia, hemorrhage with inflammatory cells infiltrated at 12 h after transplantation and they became more and more serious as time went on. The pathologic examination of rejected xenografts showed widespread intravascular thrombosis, hyperemi-a, hemorrhage, coagulative necrosis with a large number of inflammatory cells infiltrated. The stained color of vascular endothelial cells and cardiac myocytes was significantly more intensive in the xeno-grafts than that of normal BALB/c mouse hearts in the control group. The relative density values (ICAM-1/β-actin) were also significantly higher in the xenografts than that of the control group. Conclusion ICAM-1 expression in the xenografts was up-regulated, which was related with the development of the delayed xenograft rejection.