1,25-(OH)_2D_3对小鼠皮肤移植后脾T细胞亚群、MLR及NK细胞活性的影响

Effects of 1,25-dihydroxyvitamin D_3 on T-lymphocyte subsets,mixed lymphocyte reaction and natural killer cell following skin transplantation in mice

目的 探讨 1,2 5 二羟维生素D3 [1,2 5 (OH) 2 D3 ]抑制机体免疫功能的机理 ,为用于临床抗排斥治疗提供实验依据。方法 建立不同系小鼠间皮肤移植的动物模型。术日将实验小鼠随机分为四组 ,均用小鼠灌胃器给药。对照组 :每日 2 0ml/kg生理盐水 ;维生素D3 (VD3 )组 :单独应用 1,2 5 (OH) 2 D3 2 .5 μg·kg-1·d-1;环孢素A(CsA)组 :单独应用CsA 2 5mg·kg-1·d-1;VD3 +CsA组 :联合应用VD3 +CsA ,按VD3 组和CsA组用药剂量给药。术后 10d ,测定小鼠脾的T细胞亚群、单向混合淋巴细胞反应 (MLR)、自然杀伤细胞 (NK)活性。结果 VD3 组的移植皮片存活时间 (13.13±1.13)d ,明显长于对照组的 (9.75± 0 .89)d ;CD3+ 、CD4 + T细胞百分率 4 0 .19%± 4 .2 5 %、2 4 .6 5 %±3.4 7%均明显低于对照组 4 8.70 %± 7.19%、 33.5 5 %± 4 .34% ,P <0 .0 1;对BALB/C鼠的MLR(0 .95± 0 .12 )明显低于对照组 (1.19± 0 .2 2 ) ,P <0 .0 5 ;NK细胞的活性与对照组小鼠比较 ,差异无显著性。结论 1,2 5 (OH) 2 D3 能延长小鼠皮肤移植的存活时间 ,其抑制机体免疫功能的作用是通过减少CD3+ 、CD4 + T细胞的数量及抑制T细胞功能而发挥的 ,对NK细胞活性无明显影响。

Objective To evaluate the mechanism of immunosuppressive activity of 1,25-dihydroxyvitamin D_3 and provide a theoretical basis for clinical use. Methods Different inbred strain male BALB/C (H-2d) and male C57BL/6(H-2b) mice were used as skin transplantation donors and recipients, respectively. After operation C57BL/6 mice were conditioned with 1,25-dihydroxyvitamin D_3 2.5 ?μg/kg every day, Cyclosporine A (CsA) po 25 mg/kg every day separately or unitedly. Ten days after transplantation, the recipients were sacrificed, and the spleens were collected. The mouse splenic T lymphocytic subsets, mixed lymphocyte reaction (MLR), the activity of natural killer (NK) cells were determined. Results The mean survival time (MST) of skin allografts was prolonged from ( 9.75 ± 0.89 ) days to ( 13.13 ± 1.13 ) days by treatment of the recipient mice with 1,25-dihydroxyvitamin D_3. CD3 + and CD4 + subset percentage in 1,25-dihydroxyvitamin D_3 group was lower than that in control group CD3 + ( 40.19 ± 4.25 )% vs ( 48.70 ± 7.19 )%, P < 0.05 ; CD4 + ( 24.65 ± 3.47 )% vs ( 33.55 ± 4.34 )%, P < 0.01 . The stimulation index (SI) of MLR for BABL/C in 1,25-dihydroxyvitamin D_3 group was lower than in control group ( 0.95 ± 0.12 vs 1.19 ± 0.22 , P < 0.05 ). There was no significant difference in the activity of NK cells between 1,25-dihydroxyvitamin D_3 group and control group. Conclusions 1,25-dihydroxyvitamin D_3 can prolong the survival time of skin allografts in mice. The immunosuppressive effect of 1,25-dihydroxyvitamin D_3 is contributed to the decreased CD3 + and CD4 + subsets of lymphocytes and inhibition of the function of T lymphocytes.