青藤碱对肾移植大鼠急性排斥反应及T细胞增殖的影响

Effects of the alkaloid sinomenine on T cell proliferation and acute rejection in rat renal allografts

目的 探讨青藤碱 (SIN)对大鼠肾移植急性排斥反应 (AR)抑制作用的机制。方法 48只实验模型随机分为 :N .S组、SIN组、FK5 0 6组、S +F组。观察其存活时间 ,检测血肌酐 /尿素氮 (SCr/Bun)、干扰素 γ(INF γ)、肿瘤坏死因子 α(TNF α)表达水平及T淋巴细胞亚群。结果 N .S组术后 10d内死亡 ,SIN组与N .S组相比较 ,差异有显著性 (P <0 .0 5 ) ;S +F组与SIN、FK5 0 6组相比较 ,差异存在显著性。SCr/Bun :N .S组明显高于其他组 ,差异有显著性 (P <0 .0 5 ) ;SIN、FK 5 0 6组与S +F组比较差异有显著性。外周血TNF α、IFN γ表达水平、CD4+ T细胞 :N .S组的水平最高 ,与其他组相比较 ,差异有显著性 ,S +F组与SIN组或FK5 0 6相比较 ,差异有显著性 (P <0 .0 5 )。结论 SIN可能通过抑制受体鼠外周血CD4+ 细胞增殖 ,下调TNF α、IFN γ的表达水平 ,从而对同种异体大鼠肾移植起免疫抑制作用。并与FK 5 0 6有协同作用。

Objectives To evaluate the effects of the alkaloid sinomenine (SIN) on T cell proliferation and acute rejection in rat renal allografts.Methods Forty-eight recipients were divided into 4 groups at random:NS group,SIN group,FK506 group,SIN+FK506 group.Allografts of 6 recipients from each group were harvested at day 7 before end stage rejection for histological studies.The levels of TNF-α,IFN-γ and CD 4 +,CD 8 + T cell subsets in peripheral blood were measured.Results The recipients in the NS group rejected their allografs at 7th day post-operation.Treatment with either SIN or FK506 could result in minimal prolongation of grafts survival,while treatment with SIN and FK506 led to a significant prolongation of graft survival.The expression of TNF-α,IFN-γ was decreased significantly in SIN+FK506 group.The levels of CD 4 + T cell subsets in peripheral blood of the SIN+FK506 group were much lower than those of SIN group and FK506 group 7 days after transplantation.Conclusion SIN might play an immunosuppresive role in rat renal allograft models through inhibiting CD 4 + T cell proliferation and down-regulating the levels of INF-γ,TNF-α.It shows a significant synergistic effect with FK506.