中文摘要：

目的探讨同种异体间充质干细胞（MSC）移植治疗对系统性红斑狼疮（SLE）患者外周血Olf-1／EBF相关锌指蛋白（OAZ）信号通路相关基因表达水平及抗核抗体（ANA）产生的影响。方法从脐带血中分离培养MSC移植治疗10例SLE患者，采集并分离移植前、移植后1、4周患者外周血有核细胞，从细胞中提取RNA，反转录为cDNA，用实时荧光定量聚合酶链反应（PCR）技术分析不同组OAZ信号通路相关基因OAZ、分化抑制因子（Id）1、Id2、Id3 mRNA表达水平的变化。酶联免疫吸附试验（ELISA）法测定移植前后患者血清中白细胞介素（IL）-10、IL-12、IL-21、CC趋化因子配体（CCL）2、抗核抗体（ANA）浓度，并分析这些因子分泌水平与OAZ基因表达的相关性。对患者SLE疾病活动指数（SLEDAI）积分与基因表达水平进行回归分析，并以方差分析进行显著性检验。2组均数间的比较用Wilcoxon秩和检验，变量间的相关关系用Pearson相关分析。结果移植后1、4周OAZ、Id1、Id3基因的mRNA表达水平[△Ct（1周）分别为12．4±1．1、9．7±1．9、9．7±1．9、2．1±1．0；△Ct（4周）分别为13．3±1．2、10．4±1．5、10．8±1．2、2．1±1．2]较移植前（△Ct分别为11．0±0．9、7．4±2．1、7．8±2．1、0．1±1．5）均显著降低（P〈0．05）；Id2表达水平虽较移植前有低表达趋势，但差异无统计学意义。移植4周后IL-10、IL-21、ANA的水平明显低于移植前，IL-12／IL-10、CCL2高于移植前（P〈0．05），但移植后1周的水平较移植前没有差异。移植前与移植后4周OAZ mRNA表达水平变化与ANA的吸光度值和IL-21浓度比值呈负相关；与IL-12／IL-10、CCL2比值呈正相关。结论同种异体MSC移植治疗SLE可降低患者外周血中OAZ信号通路相关基因表达，同时减低多种细胞因子及ANA水平，推测OAZ信号通路可能是MSC移植治疗SLE的有效机制之一。

英文摘要：

Objective To investigate the in vivo effects of allogeneic mesenchymal stem cells transplantation （MSCT） on OAZ signaling pathway in patients with systemic lupus erythematosus （SLE）. Methods Isolated and expand human MSCs from bone marrow cells or umbilical cord of healthy donors were infused into SLE patients. Peripheral blood cells were collected from 10 pre-MSCT patients as well as 1 week and 4 week post-MSCT, and RNA was extracted and reverse transcripted to cDNA. mRNA expression levels of OAZ and Idl-3 were measured by using real-time PCR. Serum levels of IL-10, IL-12, IL-21, CCL2 and ANA were tested by ELISA. Relationships of the gene expression levels with levels of cytokines and ANA were analyzed. Results mRNA expression levels of OAZ, Idl and Id3 gene in patients with SLE were significantly decreased at week 1（△C： 12.4±1.1, 9.7±1.9, 9.7±1.9, 2.1±1.0） and at week 4 （△Ct： 13.3±1.2, 10.4±1.5, 10.8±1.2, 2.1±1.2） after MSCT when compared to those of the pre-MSCT （△Ct： 11.0±0.9, 7.4±2.1, 7.8± 2.1, 0.1±1.5 respectively, P all〈0.05）. Levels of IL-10, IL-21 and ANA were significantly lower 4 week after MSCT than those before （P〈0.05）; while level of CCL2 was higher than pre-MSCT （P〈0.05）. Cytokines and ANA levels 1 week after MSCT were not differentially changed comparing to those of the pre-MSCT. Alteration of OAZ mRNA expression levels pre- and post-MSCT were negatively correlated with changes of ANA, IL-21 levels and positively correlated with changes of IL-12/IL-10 and CCL2 levels. Conclusions The expression of genes involving in the OAZ signaling pathway is effectively reduced along with the aheration of several cytokines and ANA after allogeneic MSCT in SLE patients. OAZ signaling pathway may play an important role in MSCT treatment for SLE.