FK506对心脏移植急性排斥反应Fas和Fas-L mRNA表达的影响

INFLUENCE OF FK506 ON THE EXPRESSION OF FAS AND FAS LIGAND mRNA IN ACUTE CARDIAC ALLOGRAFT REJECTION

目的研究心脏移植急性排斥反应中供体心肌组织Fas及其配体Fas-L的mRNA的表达规律.同时探讨FK506在发挥免疫抑制作用时对二者的影响,阐述FK506在体内的作用机制.方法实验分为6组:①同系异体心脏移植组[Sprague-Dawley(SD)to SD,n=6];②同种异体移植组(Dahl to SD,n=6);③同种异体移植FK506治疗组(0.15 mg/kg·d肌肉注射,28 d,n=6),此3组观察移植心脏的存活时间.④～⑥分组情况与①～③相同,术后第5 d摘取移植心脏测定急性排斥反应强度,同时应用反转录-聚合酶链反应检测心肌Fas mRNA和Fas-L mRNA的表达水平.结果①同系异体移植组、同种异体移植FK506治疗组移植心脏存活时间(139.00±31.61)和(53.83±5.19)d明显长于同种异体移植组(7.17±0.75)d,(P＜0.001);同时,前二者的急性排斥反应强度也明显低于后者(P ＜0.001).②同种异体移植组心肌Fas mRNA和Fas-L mRNA的表达水平(Fas:0.62±0.26;Fas-L:0.34±0.12)明显高于同系异体移植组(Fas:0.39±0.16;Fas-L:0.16±0.05,P ＜0.05)和同种异体移植FK506治疗组(Fas:0.35±0.18;Fas-L:0.13±0.06,P ＜0.05).结论心脏移植急性排斥反应中FasmRNA和Fas-L mRNA的表达增强.由此可以认为,急性排斥反应中浸润性免疫细胞表面将大量表达Fas-L,从而诱导表达有Fas分子的心肌细胞的凋亡.FK506在发挥免疫抑制作用时能够阻止Fas和Fas-L mRNA的转录而抑制Fas死亡蛋白途径,抑制排斥反应的发生,延长移植心脏存活时间.

Objective To elucidate the expression of Fas and Fas ligand mRNA and the influence of FK506 on them in acute cardiac graft rejection. Methods The research was conducted with rats in six groups： ① isograft group[（Sprague-Dawley（SD） to SD, n = 6]; ② allograft group （Dahl to SD, n =6） ; ③ Allograft group with immunosuppression with FK506 （0.15 mg/ kg @ d i.m. 28 d, n =6）. The survival time of heart grafts was abserved.④-⑥ groups were designed as the first three groups. On day five, the acute rejection grade was observed and the expression level of Fas mRNA and Fas ligand mRNA of heart grafts was measured in ④-⑥ groups by semiquantitative RT-PCR. Results ① The survival time of isografts and allografts with FK506 （139.00±31.61）d and （53.83±5.19）d was markedly longer than that of allografts （7.17±0.75）d（ P 〈0. 001）, and the acute rejection grade of isografts and allografts with FK506 was markedly less than that of allografts （ P 〈0. 001）. ②Expression of Fas and Fas ligand mRNA were significantly （ P 〈0.05） increased in allograft compared with isograft hearts （Fas. 0. 62±0.26 versus 0.39 ± 0. 16, respectively; Fas ligand： 0.34 ± 0.12 versus 0. 16 ± 0.05, respectively, P 〈0.05） and allografts with FK506 （Fas： 0. 35±0.18; Fas Ligand. 0. 13±0.06, respectively, P 〈0. 05）. Conclusion The expression of Fas mRNA and Fas ligand mRNA was enhanced in acute cardiac allograft rejection. In this regard, it is possible that expression of Fas ligand by infiltrating T lymphocytes causes apoptosis of cardiacmyocytes expressing Fas. FK506 inhibites acute allograft rejection and prolongs cardiac allograft survival in part by suppressing the Fas system in cardiac allografts.