间充质干细胞联合同种异体骨髓移植治疗狼疮模型鼠的疗效观察  

Combined mesenchymal stem cells and allogenic bone marrow transplantation in treatment of MRL/ lpr mice

作　　者：张光峰[1] 张晓[1] 董光富[1] 林秋雄[1] 崔阳[1] 石韫珍[1] 罗日强[1] 李玲[1] 雷云霞[1] 林莉[1] 

机构地区：[1]广东省人民医院风湿科,广州510080

出　　处：《中华内科杂志》2008年第9期754-757,共4页Chinese Journal of Internal Medicine

基　　金：广东省自然科学基金（04003957）

摘　　要：目的观察体外扩增的骨髓源间充质干细胞联合同种异体骨髓移植治疗狼疮模型鼠的疗效，并探讨其在系统性红斑狼疮发病机制中的作用。方法将20只鼠龄为12周的雌性狼疮模型鼠按随机数字表法随机分为单纯骨髓移植组、联合Ⅰ组、联合Ⅱ组、阳性对照组，并设雄性BALB／c小鼠为阴性对照组。将体外扩增的BALB／c小鼠骨髓源间充质干细胞联合雄性C57BL／6小鼠骨髓植入狼疮模型鼠体内，测移植1个月后小鼠体内的Y染色体，并通过小鼠的体重、白细胞、尿蛋白、抗双链DNA抗体水平及终期小鼠肾脏病理和免疫荧光来评价移植的疗效。结果（1）移植30d后，可在狼疮模型鼠体内检测到Y染色体，表明移植成功。（2）单纯骨髓移植组、联合Ⅰ组、联合Ⅱ组小鼠尿蛋白和抗双链DNA抗体水平均显著下降。移植40d后联合Ⅰ组、联合Ⅱ组抗双链DNA抗体吸光度（A）值分别为0．76±0．28、0．73±0．10，与阴性对照组（0．47±0．10）相比，差异无统计学意义（P〉0．05）；单纯骨髓移植组抗双链DNA抗体水平虽有明显下降（0．91±0．27），但仍高于阴性对照组，差异有统计学意义（P〈0．05）。移植50d后单纯骨髓移植组抗双链DNA抗体A值为0．55±0．15，与阴性对照组相比差异无统计学意义（P〉0．05）。（3）各组接受移植的小鼠肾脏病理光镜下基本恢复正常，未见炎性细胞浸润及血管坏死。免疫荧光强度均弱于阳性对照组。结论单纯骨髓移植和联合间充质干细胞移植均能有效改善狼疮模型鼠的病情；间充质干细胞可加速狼疮模型鼠外周血抗双链DNA抗体和肾脏免疫复合物的清除，帮助受损器官的恢复。Objective In order to study the role of the bone marrow-derived mesenchymal stem cells （MSCs） transplanted with or without bone marrow （BM） in the treatment of lupus mice and the effect of MSCs in the onset of systemic lupus erythematosus （SLE）. Method Twenty 12-week-old female MRL/ lpr mice were randomly divided into four groups, including simple bone marrow transplantation group （SG, BM 1 × 10^7 ）, united group-1 （ UG1, BM 1 × 10^7 ＋ MSCs 1 × 10^4 ）, united group-2 （ UG2, BM 1 × 10^7 ＋ MSCs 1 × 10^6）, the positive control group （PG, no transplantation）. BALB/c mice were used as the negative control group （NG, no transplantation）. MSCs which were amplified from the bone marrow of male BALB/c mice in vitro were transplanted into the female MRL/lpr mice with or without BM. One month later Y chromosome was detected to confirm if the transplantation was successful or not. The change of weight, white blood cells, urine protein, anti-dsDNA antibody, the pathology and immunofluorescence of renal were observed to evaluate the therapeutic efficacy. Results Y chromosome was detected in all transplanted female mice. Compared with PG, urine protein concentration in SG, UG1 and UG2 significantly decreased 30 days after transplantation （P 〈 0.05 ）. 40 days after transplantation, the tite of anti-dsDNA antibodies in SG（0. 91 ± 0.27） was still higher than NG, which OD value was 0.47 ± 0. 10 （P 〈 0. 05 ）, but there was no statistical difference among UG1 （ 0. 76 ± 0. 28 ）, UG2 （0. 73 ± 0. 10 ） and NG （ P 〉 0. 05 ）. However, 50 days after transplantation, there was no marked difference of the tite of anti-dsDNA antibodies in SG （0. 55 ± 0. 15） ,UGI（0. 57 ±0. 14）and UG2（0. 58 ±0. 05） compared with NG （P 〉0. 05）. After transplantation there was no vasculitis, no inflammatory cell infiltration in matrix and no obvious intercapillary cells proliferation in the kidney. The immunofluorescence became negative or weakly positive. Conclusion MS

关 键 词：间质干细胞 红斑狼疮 系统性 骨髓移植 抗双链DNA抗体 

分 类 号：R686[医药卫生—骨科学]