多靶点联合用药抑制小鼠到大鼠异种心脏移植排斥反应

Research on the function of combined multiple targeted immunosuppressant on mouse to rat xenogenetic cardiac transplantation

目的:研究药物联合应用控制小鼠对大鼠协调性异种异位心脏移植免疫排斥反应的方法。方法:采用改良的Heron颈部套袖法建立小鼠对大鼠异种异位心脏移植模型,受体大鼠分为4组:1组,仅行异种移植不给药;2组,联合应用补体抑制剂中华眼镜蛇蛇毒因子(CCV)、环磷酰胺(CTX)、FK506;3组,将2组中CCV剂量加倍,其它药物用量不变;4组,在2组用药组合基础上再加用前列腺素E1(PGE1)。观察移植供心存活时间,并检测受体大鼠血清补体总活性(CH50)改变、移植供心病理改变。结果:异种移植术后各组小鼠供心平均存活时间:1组为(2.25±0.52)d,2组为(4.25±1.25)d,3组为(3.75±0.65)d,4组为(6.92±2.46)d。2、3、4组补体活性明显降低。移植供心HE病理显示1组为典型超急性排斥反应改变,4组出现急性排斥反应改变。结论:在小鼠对大鼠的协调性异种移植中,CCV+CTX+FK506+PGE1联合应用可明显抑制异种超急性排斥反应的发生。

Objective: To study the methods of controlling the immune-rejection in mouse-to-rat concordant xenogenetic cardiac transplantation by combined using of several drugs.Methods: A mouse-to rat heterotopic cardiac xenografts model was established by improved Heron’s cuff technique in neck.Recipient rat was divided into 4 groups respectively as following: Group 1 received xenograft without treatment;Group 2 was treated with CCV+CTX+FK506;The dose of CCV in Group 3 was doubled;Group 4 was treated with CCV+CTX+FK506+PGE1.The cardiac survival time was observed and the level of complement(CH50) in rat was examined.Moreover the xenografts were examined by optical microscope.Results: The average cardiac survival time of Group 1 was(2.25±0.52)d,and Group 2 was(4.25±1.25)d,Group 3 was(3.75±0.65)d,as well as Group 4 was(6.92±2.46)d.The level of complement in Groups 2,3,4 were lower than Group 1.A typical hyperacute rejection phenomenon could be seen by optical microscope in Group 1.However a typical acute rejection could be seen in Group 4.Conclusion: In mouse-to-rat concordant xenotransplantation,combined using of CCV,CTX,FK506 and PGE1 can suppress the occurrence of the hyperacute rejection.