白细胞介素7受体α干预小鼠异基因骨髓移植后急性移植物抗宿主病的初步研究

Preliminary study on IL-7Rα intervening acute graft-versus-host disease after mice allogeneic bone marrow transplantation

目的建立小鼠异基因骨髓移植后急性移植物抗宿主病（aGVHD）模型，探讨外源性白细胞介素7（IL-7）受体α（IL-7Rα）干预小鼠aGVHD的疗效及可能机制。方法以BALB／C（H-2α）雌性小鼠为受鼠，将受鼠分为单纯照射组、照射移植组、IL-7Rα干预组3组，每组10只，均接受9Gy^60Co进行全身照射，取C57BL／6（H-2α）供鼠骨髓细胞1×10^7个和脾细胞2X10，个经尾静脉输注给受鼠，观察受鼠的体征、造血功能恢复及生存时间的变化，并进行病理学、嵌合体及细胞因子水平的检测。结果单纯照射组小鼠照射后逐渐死亡；照射移植组和IL-7Rα干预组小鼠移植后出现了典型的aGVHD症状，IL-7Rα干预组体征较照射移植组轻，生存时间较长，IL-7Rα干预组外周血白细胞计数＋14、＋21、＋28天造血功能恢复情况与照射移植组比较[（4．53±0．21）×10^9／L、（3．63±0．06）×10^9／L、（4．31±0．04）×10^9/L与（1．81±0．05）×10^9／L、（1．32±0．04）×10^9／L、（1．76±0．04）×10^9／L1，差异有统计学意义（t值分别为0．237、0．108、0．359，均P〈0．05）；肝、脾、皮肤组织的病理学结果显示，IL-7Rα干预组较照射移植组轻；嵌合体植入成功；移植后＋7天血浆IL-7水平显著增高，随时间变化IL-7R饯干预组＋14、＋21天IL．7浓度与照射移植组比较[（194．32±1．02）、（131．63±1．54）pg／ml与（330．24±8．08）、（184．09±2．05）Pg／ml]，差异有统计学意义（t值分别为1．590、1．285，均P〈0．05）。结论建立了稳定的aGVHD小鼠模型；在aGVHD发生早期血浆IL-7水平显著增高汐h源性IL-7 Rα可降低血浆IL-7水平，从而减轻异基因骨髓移植后aGVHD的发生。

Objective To establish a mouse model of acute graft-versus-host disease （aGVHD） after allogeneic bone marrow transplantation, and using exogenous interleukin-7 receptor alpha （IL-7Rα） intervene mice aGVHD and analyse its possible mechanism. Methods The BALB/C （H-2d） female mice as recipients were grouped by rat： the irradiation group （group A）, irradiation transplantation group （group B） and IL-7Rα in the intervention group （group C）, each 10. ALL mice were accepted 9 Gy ^60Co total body irradiation, 1×10^7 bone marrow cells and 2×10^7 spleen cells of donor C57BL/6 （H-2b） via the tail vein were infused to recipient mice. The signs of the recipient mice,hematopoietic functional recovery and survival time of change, and pathology, chimerism and cytokine levels in check were observed. Results Mice in A group after irradiation were gradually death, in group B and group C mice after transplantation had typical aGVHD symptoms, but lighter signs and a longer survival time of Group C than in group B. WBC count in Group C was ＋14 d （4.53± 0.21） ×10^9/L, ±21 d （3.63±0.06） ×10^9/L, ±28 d （4.31±0.04） ×10^9/L, was hematopoietic recovery compared with Group B [＋14 d （1.81±0.05） ×10^9/L, ±21 d （1.32±0.04） ×10^9/L, ±28 d （1.76±0.04） ×10^9/L], the difference was statistically significant （t = 0.237, 0.108, 0.359, P 〈 0.05）. The pathological results of liver, spleen, skin histopathology in group C were better than group B. Chimera implants, plasma IL-7 levels after transplant ＋7 d, concentration was significantly increased. IL-7 concentration in group C was ＋14 d （194.32±1.02） pg/ml, ＋21 d （131.63±1.54） pg/ml and in group B was ＋14 d （330.24±8.08） pg/ml, ＋21 d （184.09±2.05） pg/ml, the difference was statistically significant （t = 1.590, 1.285, P 〈0.05）. Conclusion The stable aGVHD mouse model was established. In aGVHD early, plasma IL-7 levels were significantly increased. Exogenous IL-7Rα can reduce the plasma IL-7 levels, thereby reducing the incidence of aGVHD after allogeneic bone marrow transplantation.