混合造血干细胞移植治疗小鼠系统性红斑狼疮的实验研究  

Experimental study of hematopoietic stem cell transplantation for the treatment of murine systemic lupus erythematosus

作　　者：倪丽[1] 刘冠贤[1] 董光富[2] 石咏军[1] 崔晓[1] 

机构地区：[1]广东省惠州市中心人民医院肾内科,516001 [2]广东省人民医院风湿科

出　　处：《中华风湿病学杂志》2010年第8期530-534,585,共6页Chinese Journal of Rheumatology

基　　金：广东省自然科学基金（5008540）;广东省惠州市技术研究与开发资金项目（2008G50）

摘　　要：目的探讨纯化同基因和异基因混合造血干细胞移植治疗狼疮鼠的效果。方法36只MRL／Ipr小鼠随机分为对照组、药物组、混合移植组（同基因与异基因比例为1：5、1：10、1：15），以及异基因组，每组6只。分离纯化造血干细胞，按不同比例混合后，尾静脉注射到^60Co照射预处理后的MRL／Ipr小鼠，药物组每天腹腔注射地塞米松1mg·kg^-1·d^-1，对照组每天腹腔注射等量生理盐水。检测小鼠尿蛋白、外周血肌酐、白细胞，采用重复测量的方差分析进行统计学处理。酶联免疫吸附试验（ELISA）检测抗核抗体。光镜、电镜、免疫荧光检测肾组织病理变化。结果对照组血肌酐[移植后7-9周为（165±20）μmol／L]、尿蛋白随时间的增加而上升，各移植组[分别为（50±8）、（52±7）、（52±9）μmol／L]和药物组[（48±8）μmol／L]随时间增加而降低，其中混合移植组和药物组较异基因组下降明显，差异有统计学意义（P〈0．05），各混合移植组、药物组间差异无统计学意义（P〉0．05）。对照组肾组织病理损伤最重，病理损伤评分多为3～4度；异基因组肾组织病理损伤较重，多为2度；药物组和混合移植组病理损伤多为1～2度。结论混合造血干细胞移植可有效纠正和控制狼疮鼠的大量蛋白尿，改善狼疮鼠的肾脏病变、是一种较安全、有效的治疗狼疮鼠的方法。Objective To study the effect of mixed purified autogenic and allogeneic hematopoietic stem cell transplantation for the treatment of systemic lupus erythematosus. Methods Thirty-six MRL/Ipr mice were randomly divided into the control group, the study group,the mixed group （the ratio of autogenic to allogeneic cells was 1：5, 1：10, 1 ：15）, and allogeneic transplantation group. Isolation and Purification of hematopoietie stem cells, mixed in different proportions were infused intravenously after ^60Co irradiation. The study group were treated with daily intraperitoneal infusion of dexamethasone 1 mg·kg^-1·d^-1, while the control group were treated with intraperitoneal infusion of equivalent volume of saline daily. The changes of serum creatinine level, the urine protein excretion of the mice and blood WBC count were compared. Repeat measures ANOVA was used for data analysis. ELISA was used for anti-nuclear antibody detection Light microscopy, electronic micros-copy, imnmnofluorescence were applied to detect the pathological changes in renal tissue. Results Serum creatinine and urine protein excretion levels increased with time in the ontrol group, while those of the transplant group and the study group decreased. The reduction in mixed transplantation group and the study group was more evident compared with that of the allogeneic group. The difference was statistically significant （P〈0.05）, but there was no significant difference between the mixed transplantation groups and the study group （P〉0.05）. The histopathologic damage was most serious in the control group as pathological injury seore of most mice were in grade 3 or 4. The majority of the histopathologic damage of the allogeneic group was in grade 2. Most f pathological damage of the study drug group and the mixed transplantation group were grade 1 or 2. Conclusion Mixed hematoopoietic stem cell transplantation for the treatment of murine systemic lupus erythematosus can effectively correct heavy proteinuria in murine systemic lupus e

关 键 词：红斑狼疮 系统性 造血干细胞移植 小鼠 

分 类 号：R457.7[医药卫生—治疗学]