中文摘要：

目的探讨脐带MSCs移植对MRL／lpr鼠狼疮发病是否有预防作用及可能的机制。方法14只10周龄的雌性MRL／lpr小鼠应用随机数字表法分为2组：脐带MSC组每只尾静脉注射1×10^6脐带MSCs，对照组尾静脉注射等量的PBS；每4周Bradford法检测尿蛋白；28周龄时处死小鼠，ELISA检测血清抗dsDNA抗体及IL-17，流式细胞术检测脾脏Th17及调节性T细胞百分率。采用t检验及Pearson相关性分析。结果脐带MSC组小鼠出现蛋白尿的时间比对照组延迟4周。28周龄时，脐带MSCs组小鼠尿蛋白定量（24h）和脾脏质量显著小于对照组[（1．78±0．17）mg与（4．77±0．98）mg，t=2．99，P〈0．05和（0．149±0．009）g与（0．273±0．052）g，t=2．33，P〈0．05]；血清抗dsDNA抗体及IL-17水平与对照组相比也有下降趋势。脐带MSC组小鼠脾脏Th17细胞的百分率和绝对数与对照组相比均显著减少[（0．90±0．19）％与（2．81±0．50）％，t=3．54，P〈0．01和（3．7±0．8）×10^5与（19．3±3．7）×10^5，t=4．12，P〈0．01]；而脾脏调节性T细胞的百分率在脐带MSCs移植之后则升高。脐带MSC组小鼠脾脏Th17／调节性T细胞比例显著低于对照组（0．11±0．03与0．50±0．09，t=4．23，P〈0．01）。MRL／lpr小鼠脾脏Thl7调节性T细胞比例与尿蛋白定量（24h）（r=0．73，P〈0．01）及血清抗dsDNA抗体水平呈正相关（r=0．59，P〈0．05）；血清IL-17水平也与尿蛋白定量（24h）（r=0．78，P〈0．01）及血清抗dsDNA抗体水平呈正相关（r=0．56，P〈0．05）。结论脐带MSCs移植可能通过调节Th17调节性T细胞平衡延缓MRL／Ipr小鼠发病和疾病进展。

英文摘要：

Objective To explore the preventive effect of early umbilical cord mesenchymal stem cells （UC-MSCs） transplantation on MRL/lpr mice and the underly mechanisms. Methods Fourteen 10-week-old MRL/lpr mice were labeled and numbered. They were randomly divided into 2 groups by using random number table and injected with 1 ×10^6 UC-MSCs or PBS via tail vein respectively. Proteinuria was measured with Bradford method every 4 weeks. All mice were sacrificed at the age of 28 weeks, with the level of serum anti- dsDNA antibody and IL-17 detected by enzyme linked immunosorbent assay （ELISA）. Splenic Thl7 cells, as well as regulatory T ceils （Treg） were examined by flow cytometry. Data were analyzed with t test and Pearson＇s correlation test. Results The onset of proteinuria was delayed for 4 weeks in UC-MSC-treated group compared with that in the control group. At the age of 28 weeks, the 24 hour proteinuria [（1.78±0.17） mg vs （4.77±0.98） mg, t=2.99, P〈0.05] and the spleen weight [（0.149±0.009） g vs （0.273±0.052） g, t=2.33, P〈0.05] in UC-MSC- treated group were significantly lower than those irf the control group. There was also a trend of the decline of serum anti-dsDNA antibody and IL-17 level after UC-MSCs transplantation. Compared with those in the control group, both the percentage and the absolute number of Thl7 cells were significantly decreased in UC-MSC- treated group [（0.90±0.19）% vs （2.81±0.50）%, t=3.54, P〈0.01 and （3.7±0.8）×10^5 vs （19.3±3.7）×10^5, t=4.12, P〈0.01]. Meanwhile, the percentage of Treg elevated after UC-MSCs treatment. The ratio of Thl7/Treg was significantly lower in UC-MSC-treated group than that in the control group （0.11±0.03 vs 0.50±0.09, t=4.23, P〈0.01）. Both the ratio of Thl7/Treg （r=0.73, P〈0.01; r=0.59,p〈0.05） and serum IL-17 level （r=0.78, P〈0,01; r=0.56, P〈0.05） was positively correlated with the level of 24 hour proteinuria and anti-dsDNA antibody respectively in MRL/Ipr mice. Conclusion Early UC-MSC