小鼠造血干细胞移植后移植物抗宿主病与内皮细胞损伤的关系

目的 探讨异基因造血干细胞移植后移植物抗宿主病(GVHD)与内皮细胞损伤的关系.方法 以C57BL/6小鼠为供者、Balb/c小鼠为受者,分4组进行异基因造血干细胞移植,每组受者15只:对照组(仅输入磷酸盐缓冲液)、单纯骨髓移植组(仅输入骨髓单个核细胞)、GVHD组(输入骨髓单个核细胞和脾细胞)、GVHD减轻组(在GVHD组基础上加用环孢素A).分别于移植后不同时间观察受者的表现,检测外周血中内皮细胞及组织病理学变化.结果 术后第5天,各组受者均无典型的GVHD表现及组织病理学改变;术后第9天,GVHD组受者出现明显的GVHD的表现及病理学改变,并于15 d内全部死亡.术后第5天,单纯移植组、GVHD组和GVHD减轻组受者的外周血中内皮细胞数分别为(11.51±7.40)、(7.34±1.26)和(7.36±0.16)个/μl,三组间差异均无统计学意义(P＞0.05);术后第9天,内皮细胞数分别为(10.49±5.61)、(153.64±35.35)及(47.82±4.69)个/μl,三组间差异均有统计学意义(P＜0.05).术后第5天,单纯移植组、GVHD组、GVHD减轻组受者GVHD靶器官组织病理学评分分别为3.33±0.58、4.33±1.53及4.0±1.73,三组间差异均无统计学意义(P＞0.05);术后第9天,评分分别为3.33±1.15、10.0及4.33±0.58,三组间差异均有统计学意义(P＜0.05);术后第14天,评分分别为2.33±1.25、10.33±2.58和3.33±1.15,三组间差异均有统计学意义(P＜0.05).结论 GVHD的发生再次引起内皮的损伤,同时损伤的内皮加重了GVHD.

Abstract：

Objective To study the relationship between graft-versus-host disease (GVHD) and endothelium injury following hematopoietic stem cells transplantation in mice. Methods C57BL/6 mice as donors and Balb/c mice as recipients were randomly divided into 4 groups: control group, bone marrow transplantation group, GVHD group, GVHD mitigation group. The clinical manifestations,circulating endothelial cells and tissue pathological changes were observed at different time points after transplantation. Results No manifestations of GVHD were found in each group at the day 5, while those were found in GVHD group at the day 9 and all died within 15 days. The counts of endothelial cells in peripheral blood showed no significant difference at the day 5 between GVHD group (7. 34 ±1.26 cells/μl) and bone marrow transplantation group (11.51 ± 7. 40 cells/μl) or GVHD mitigation group (7. 36 ± 0. 16 cells/μl), while among three groups there was statistically significant difference at the day 9 (GVHD group: 153. 64 ± 35. 35 cells/μl vs bone marrow transplantation group: 10. 49 ±5. 61 cells/μl and GVHD mitigation group: 47. 82 ± 4. 69 cells/μl). The scores of pathological aGVHD had no significant difference at the day 5 between GVHD group (4. 33± 1. 53) and bone marrow transplantation group (3. 33 ± 0. 58) or GVHD mitigation group (4. 00 ± 1.73), while among three groups there was statistically significant difference at the day 9 (GVHD group: 10. 0 vs bone marrow transplantation group: 3. 33 ± 1.15 or GVHD mitigation group: 4. 33 ± 0. 58) and at the day 14 (GVHD group: 10. 33 ± 2. 58 vs bone marrow transplantation group: 2. 33 ± 1.25 or GVHD mitigation group 3. 33 ± 1.15). Conclusion Occurrence of GVHD causes endothelial damage again and injured endothelium worsens the GVHD.

Relationship between graft-versus-host disease and endothelium injury following hematopoietic stem cells transplantation in mice

Objective To study the relationship between graft-versus-host disease (GVHD) and endothelium injury following hematopoietic stem cells transplantation in mice. Methods C57BL/6 mice as donors and Balb/c mice as recipients were randomly divided into 4 groups: control group, bone marrow transplantation group, GVHD group, GVHD mitigation group. The clinical manifestations,circulating endothelial cells and tissue pathological changes were observed at different time points after transplantation. Results No manifestations of GVHD were found in each group at the day 5, while those were found in GVHD group at the day 9 and all died within 15 days. The counts of endothelial cells in peripheral blood showed no significant difference at the day 5 between GVHD group (7. 34 ±1.26 cells/μl) and bone marrow transplantation group (11.51 ± 7. 40 cells/μl) or GVHD mitigation group (7. 36 ± 0. 16 cells/μl), while among three groups there was statistically significant difference at the day 9 (GVHD group: 153. 64 ± 35. 35 cells/μl vs bone marrow transplantation group: 10. 49 ±5. 61 cells/μl and GVHD mitigation group: 47. 82 ± 4. 69 cells/μl). The scores of pathological aGVHD had no significant difference at the day 5 between GVHD group (4. 33± 1. 53) and bone marrow transplantation group (3. 33 ± 0. 58) or GVHD mitigation group (4. 00 ± 1.73), while among three groups there was statistically significant difference at the day 9 (GVHD group: 10. 0 vs bone marrow transplantation group: 3. 33 ± 1.15 or GVHD mitigation group: 4. 33 ± 0. 58) and at the day 14 (GVHD group: 10. 33 ± 2. 58 vs bone marrow transplantation group: 2. 33 ± 1.25 or GVHD mitigation group 3. 33 ± 1.15). Conclusion Occurrence of GVHD causes endothelial damage again and injured endothelium worsens the GVHD.