骨化三醇在抑制大鼠同种肢体移植排斥反应中的作用

目的 探讨应用骨化三醇(1,25-二羟维生素D;简称:VD5)在抑制肢体移植排斥反应中的作用.方法 以Wistar大鼠为供者,SD大鼠为受者,建立同种肢体移植模型.随机将受者分为4组,每组12只.(1)对照组:术后不用免疫抑制剂,仅以15 ml·kg-1·d-1.生理盐水灌服.(2)他克莫司(FK506)组:将FK506用生理盐水稀释为0.5 mg/ml,术后前2周的用量为1.0 mg·kg-1·d-1,术后第3周起,每周灌服2次.(3)VD3组:将骨化三醇用生理盐水稀释为0.125 μg/ml,术后用量为2.5μg·kg-1·d-1,连续灌服4周.(4)VD3+FK506组:术后联合应用骨化三醇及FK506,用药方法和用量与FK506组和VD3组相同.术后观察各组受者移植肢体排斥反应发生的时间和存活时间;流式细胞仪检测T淋巴细胞亚群CD4+、CD8+细胞的百分率.结果 对照组、FK506组、VD3组以及VD3+FK506组肢体移植后排斥反应发生的时间分别为:(3.50±0.50)d、(13.13±1.50)d、(10.63±0.38)d和(29.25±0.63)d;移植肢体的存活时间分别为:(8.50±0.50)d、(26.25±1.50)d、(17.25±0.38)d和(62.00±0.63)d;与对照组比较,VD3组排斥反应发生的时间和移植肢体的存活时间均明显延长,差异有统计学意义(P＜0.01);VD3+FK506组抗排斥反应效果更佳,与FK506组和VD3组比较,差异有统计学意义(P＜0.01).VD3组T淋巴细胞亚群CD4+/CD8+细胞的比值明显低于对照组,VD3+FK506组又明显低于VD3组和FK506组(P＜0.01).结论 骨化三醇能明显减轻同种肢体移植排斥反应,延长移植肢体的存活时间;骨化三醇与FK506联合应用效果更佳,二者具有协同作用.

Effects of Calcitriol on allograft acute rejection in rat limb transplantation

Objective To investigate the effects of Calcitriol (1, 25-dihydroxyvitamin D3, VD3) on rejection of allogenic limb transplantation. Methods Rat allogenic limb transplantation model (Wistar rats→ SD rats) was established. Recipients were divided into 4 groups randomly: 12 recipients received normal saline solution (15 nag·ml-1·d-1 orally) (group A); 12 recipients received FK506 solution (1.0 mg·ml-1·d-1) for 2 weeks and then 1.0 mg/ml twice a week (group B); 12 recipients received Calcitriol solution (2.5 μg-1ml-1·d-1) for 4 weeks (group C); 12 recipients received FK506 solution and Caleitriol solution (group D). Mean survival time (MST) of the limb grafts and mean time of rejection were observed. Flow cytometry was used to detect the expression of CD4+ and CD8+ in T lymphocytes. Results Mean time of rejection was (3.50±0.50) d in group A, (13.13±1.50) d in group B, (10.63±0.38) d in group C and (29.25±0.63) d in group D. MST of the limb grafts in groups A, B, C and D was (8.50±0.50)d, (26.25±1.50)d, (17.25±0.38)d and (62.00±0.63)d, respectively. There was significant difference between group A and group C in MST of the limb grafts and mean time of rejection (P＜0.01). Significant differences were also observed between group D and groups B, group C in these 2 indexes (P＜0.01). The percentage of CD4+ and CD8+ T lymphocytes in group C was less than that in group A (P＜0.01), and that in group D was less than that in group B and group C (P＜0.01). Conclusions Caldtriol can reduce the occurrence of reaction of allogenie limb transplantation and prolong MST of the grafts. Because of synergistic effects, Calcitriol combined with FK506 is more effective.