细胞因子在心脏移植急性排斥反应中的表达及其作用机理

Expression of cytokines in acute heart transplantation rejection

目的 观察同种大鼠心脏移植急性排斥反应中 ,局部细胞因子网络的变化及其机理。 方法 健康雄性Wistar大鼠 (受体 )和SD大鼠各 48只 ,将接受移植心脏的Wistar大鼠分 4组 ,每组12只。A组 :对照组 ;B组 :抗白介素 2单克隆抗体 (IL 2Mab)组 ;C组 :环孢菌素A(CsA)组 ;D组 :IL 2Mab加CsA组。 4组大鼠分别静脉给予生理盐水、抗白介素 2单克隆抗体及口服CsA、静脉给予抗白介素 2单克隆抗体加口服CsA ,采用改良的移植术式建立移植模型。常规监测排斥反应发生情况。应用RT PCR的方法于术后第 1、3、5、7、9、11、14天动态检测移植物局部细胞因子IL 1β、IL 2、CD2 5、IL 4、IL 5、IL 6、IL 10、TNFα、IFNγ的表达水平。 结果 移植心脏存活时间 ,A组为 (8 3± 1 7)d ;B组为(2 9 2± 7 1)d ;C组为 (2 6 4± 5 7)d ;D组为 (5 5 0± 11 6 )d。B、C、D组移植心脏存活时间显著延长 ,与A组相比 ,差异有极显著性意义 (P <0 0 1)。存活时间较长的移植心脏的淋巴细胞浸润和心肌坏死的程度比存活时间较短的心脏明显减轻。IL 1β的表达在各组均较高 ;IL 4、IL 5、IL 6、IL 10的表达水平在移植心脏存活时间较长的组较高 ;而IL 2、CD2 5、IFN γ、TNFα的表达则相对较低 ;4组相比差异有显著性意义 (P <0 .0 5 )。 结?

Objective To observe the expression and changes of local cytokines network in rat heart transplantation so as to determine the role of cytokines in acute rejection of rat heart transplantation. Methods The Wistar rats (receptor) were divided into four groups: group A(control, n =12),group B(IL 2 Mab treated, n =12),group C [Cyclosporine A (CsA) treated, n =12] and group D(IL 2Mab+CsA treated, n =12). Hearts from SD rats were transplanted into a cervical location in Wistar. The local expression of IL 1β,IL 2,CD25,IL 4,IL 5,IL 6,IL 10,TNFα,IFNγ was examined at 1,3,5,7,9,11,14 days after operation by reverse transcription polymerase chain reaction (RT PCR). Results Allografts survival time was (8 3±1 7) days in group A, (29 2±7 1) days in group B, (26 4±5 7) days in group C, (55 0±10 6) days in group D. The expression of IL 1β,IL 4,IL 10, IFNγ was up regulated, and the expression of IL 2, CD25, IL 5, IL 6, TNFα was significantly inhibited in group A. The expression of IL 1β, IL 5, IL 6, IL 10, IFNγ was up regulated, and the expression of IL 2, IL 4, TNFα was significantly down regulated in group B. The expression of IL 1β, IL 2, CD25, IL 5, TNFα?IFNγ was up regulated, and the expression of IL 4, IL 6, Il 10 was significantly down regulated in group C. The expression of IL 4, IL 5, IL 6, IL 10 was up regulated, and the expression of IL 1β, IL 2, CD25, IFNγ, TNFα was significantly down regulated in group D. Conclusions Cytokines play an important role in the development of acute transplantational rejection. Different cytokines play different roles in different local environments; the main principle possibly is immune deviation.