他克莫司和来氟米特合用抑制大鼠心脏移植排斥反应及T淋巴细胞增殖

Combined use of tacrolimus and leflunomide in prevention of acute rejection and T cell proliferation in cardiac allografts of rats

目的 评价他克莫司 (FK5 0 6 )和来氟米特联合应用对大鼠心脏移植排斥反应的抑制作用。方法 将实验动物随机分为对照组、FK5 0 6组、来氟米特组以及FK5 0 6与来氟米特合用组 ,观察移植心存活时间 ,于术后 7d切取部分移植心做病理检查 ,并测定各组受者外周血T淋巴细胞亚群及肝、肾功能。结果 不用免疫抑制剂的对照组移植心存活时间为 ( 7.14± 1.0 7)d ,单用FK5 0 6的组为( 11.14± 1.73)d ,单用来氟米特的组为 ( 11.2 9± 1.80 )d ,两药合用组为 ( 14 .0 0± 2 .4 9)d ,合用组的病理切片提示排斥反应明显轻于两药单用组。术后 7d ,合用组外周血T淋巴细胞亚群中 ,CD4 +细胞明显低于两药单用组 (P <0 .0 5 ) ,而CD8+细胞各组间的差异无显著性 ;各组间肝、肾功能的差异也无显著性。结论 FK5 0

Objective To evaluate the role of combined use of tacrolimus and leflunomide (Lef) in prevention of acute allograft rejection in rats.Methods The rats were randomly divided into control group, tacrolimus treated group, Lef treated group and tacrolimus +Lef treated group. The drugs were given by gavage from day 0 to day 9 after transplantation. Graft survival was observed. Some cases of allografts were examined histologically 7 days after transplantation. At the same time, the levels of CD4 + , CD8 + T cell subsets in peripheral blood were examined by using flow cytometry and the hepatic function as well as renal function of recipents were also tested. Results The graft survival time in control group, tacrolimus treated group, Lef treated group and tacrolimus+Lef treated group was 7.14 ± 1.07 days, 11.14 ± 1.73 days, 11.29 ± 1.80 days and 14.00 ± 2.49 days, respectively. The histological study revealed the rejection in the tacrolimus+Lef treated group was slighter than the tacrolimus treated group and Lef treated group. The levels of CD4 + T cell subsets in the peripheral blood of the tacrolimus+Lef treated group were much lower than those of the tacrolimus treated group and Lef treated group 7 days after transplantation. The levels of CD8 + T cell subsets and the hepatic function and renal function had no significant difference.Conclusion Combined use of tacrolimus and Lef had better effect in prevention of acute rejection in allograft rats than monotherapy without increasing side effects.