FK506对大鼠心脏移植细胞凋亡的作用

Effects of FK506 on the apoptosis in acute cardiac allograft rejection in rats

目的 观察大鼠心脏移植急性排斥反应中的细胞凋亡现象及FK5 0 6对它的影响。方法 进行 48次SD→Wistar的大鼠颈部心脏移植 ,用苏木素 伊红 (HE)染色和原位末端标记(TUNEL)技术检测移植心切片 ,进行排斥反应的病理分级并计算凋亡指数 (AI)。结果 移植心的细胞凋亡主要发生于心肌细胞 ;FK5 0 6能明显减少心肌细胞的凋亡 ,减轻移植心的组织损伤。移植后第 3、5、7天AI对照组分别为 3.73± 2 .32、8.30± 2 .97、10 .2 2± 5 .5 2 ;FK5 0 6治疗组为 1.2 7± 1.2 0、2 .89± 2 .18、3.11± 1.6 8;两组比较差异有非常显著性 (P <0 .0 1)。结论 细胞凋亡是心脏移植急性排斥中组织损伤的重要机制 ;FK5 0 6能明显抑制心肌细胞凋亡 ,这可能是FK5 0 6发挥免疫抑制作用的重要方面。

Objective To investigate the effects of FK506 on apoptosis during acute rejection of cardiac allograft in rats. Methods Forty-eight Wistar rats underwent heterotopic heart transplantation in the cervical portion from disparate SD rats. The cardiac grafts were harvested at 3,5 or 7 days after transplantation. The cardiac allograft sections were subjected to the HE staining and in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) for histopathological rejection grade and apoptotic index (AI). Results Apoptosis mainly occurred in cardiac myocytes throughout allograft rejection. FK506 could markedly reduce myocyte apoptosis and abate the damage to the graft tissue. The AI at 3、5 or 7 days post-transplantation were 3.73±2.32,8.30±2.97,10.22±5.52, in control group and 1.27±1.20,2.89±2.18, 3.11±1.68 in FK506 group respectively with the difference between them being significant.Conclusions Apoptosis is an important mechanism of cell death in acute cardiac allograft rejection in rats. FK506 can apparently inhibit the apoptosis of cardiac myocytes, which may be an important way of its immunosuppressive actions.