氨基胍对大鼠心脏移植急性排斥期细胞凋亡与诱导型一氧化氮合酶的影响

Effect of aminiguanidine on inducible iNOS and cell apoptosis during acute cardiac allograft rejection in rats

目的:探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对大鼠心脏移植后急性排斥反应期细胞凋亡的影响。方法:分3组建立大鼠腹腔异位心脏移植模型:同系移植组、同种移植组、同种移植后AG治疗(应用AG(600mg/(kg·d))皮下注射)组。各组分别在术后第3d,5d,7d采集移植心肌的心室组织,观察移植心脏排斥反应情况,细胞凋亡情况及心肌组织中iNOS活性的变化。结果:①同种移植组和同种移植后AG治疗组排斥反应差异有统计学意义(χ2分别为11.98,12.70,P<0.05);②心脏移植后各级排斥反应中均可见细胞凋亡的存在,且随着心脏移植排斥反应的加重,心肌细胞凋亡的量也在增加;③同种移植后AG治疗组与同种移植组相比各时间段iNOS活性均明显升高,而与同系移植组相比,差异无统计学意义。结论:AG可以通过抑制心脏移植术后急性排斥期的iNOS活性,从而抑制细胞凋亡,保护移植心脏的功能。

Aim ： To investigate the effects of a selective iNOS-blocking drug （aminiguanidine,AG） on the cell apoptosis during acute cardiac allograft rejection in rats. Methods： Rat heterotopic cardiac transplantation model was used. Group A： heart transplantation group with Wistar rat donor and Wistar rat recipient was given physiological saline（ 1 ml） subcutaneously once per day; Group B： heart transplantation group with SD rat donor and Wistar rat recipient was given physiological saline（ 1 ml） subcutaneously once per day; Group C： heart transplantation group with SD rat donor and Wistar rat recipient was treated with AG subcutaneously once per day. In each group the transplanted hearts were harvested on the 3rd, 5th, and 7th day, respectively. The cardiac allograft rejection, the cell apoptosis and iNOS activity were detected. ReSultS ： The pathological grades of cardiac allograft rejection in group B and C had significant difference （ P 〈 0.05 ）. The apoptotic index increased with the severity of the cardiac allograft rejection. Compared with Group B, iNOS activities in Group C obviously increased at all the time stage. Conclusion： Apoptosis during acute rejection can be relieved by preconditioning with AG, and the function of the transplanted hearts can be protected.