摘要
目的探讨骨髓间充质干细胞（MSCs）治疗胶原诱导型关节炎（CIA）疗效及可能治疗机制。方法分离培养C57BIJ6小鼠MSCs。健康对照组DBA-1小鼠3只（第0天和第21天尾静脉输注生理盐水0．2m1）15只牛Ⅱ型胶原诱导的CIA小鼠随机分为CIA对照组（第0天和第21天尾静脉输注生理盐水0．2ml）、预防组（第0天输注MSCs1×10^6细胞数／200μl）和治疗组（第21天输注MSCs12×10^6细胞数／200μl）。另设健康对照组（不诱导CIA，第0天和第21天尾静脉输注生理盐水0．2ml）。疗效观察包括关节炎指数（AI）评分，关节病理分析，酶联免疫吸附试验（ELISA）测血清肿瘤坏死因子（TNF）-α，白细胞介素（IL）-1β水平，流式细胞术检测脾脏和淋巴结CD4^＋CD25^＋Foxp3^＋T淋巴细胞百分率等。结果①预防组和治疗组AI、关节病理评分明显下降（P〈0．05）；②健康对照组、预防组和治疗组血清TNF—α和IL-1β水平降低（P〈0．05），与AI呈显著正相关（P〈0．05），TNF—α与关节病理评分呈显著正相关（r=0．61，P〈0．01）；③治疗组小鼠脾脏和淋巴结中调节性T细胞明显升高（P〈0．05）。结论MSCs治疗CIA有效，抑制TNF—α和IL-1β和上调调节性T细胞可能是MSCs治疗CIA有效的机制。
Objective To investigate the effect of bone marrow-derived mesenehymal stem cells （MSCs） on collagen-induced arthritis （CIA） and the possible mechanisms. Methods NSCs from C57BL/6 mice bone marrow were isolated and expanded. Three DBA-1 mice were as normal control group （Sodium Chloride injected on day 0 and 21） after primary immunization. After the bovine collagen Ⅱ indueed-CIA models were established, fifteen male mice were randomly divided into 3 groups according to treatment regimens： CIA control group （0.2 ml Sodium Chloride injected through caudal vein on day 0 and 21 ）, prevention group （ 1×10^O6 cells NSC on day 0） and treatment group （ 1×10^6 cells MSC on day 21 after primary immun- ization）. The observed parameters included arthritis index （AI）, articular pathology changes, levels of serum TNF-α, IL-1β detected by ELISA. In addition, the percentage of CD4^＋CD25^＋Foxp3.Treg eells（Tregs） in CD4^＋ T eells of spleen or lymphoid node from mice were also analyzed by flow eytometry （FCM）. Results （2） The AI and articular pathological score of the prevention group and treatment group were lower than the CIA control group （P〈0.05）. （3） The levels of serum TNF-α and IL-1β of normal control, prevention group and treatment group were significantly decreased compared with CIA control group （P〈0.05）, and positively correlated with A1 or articular pathological score （P〈0.05）. （3）The percentage of Tregs from spleen and lymph nodes was significantly increased in MSCs treated mice （P〈0.05）. Conclusion MSCs transplantation is effective for CIA and suppression of TNF-α, IL-1β and up-regulation of Tregs by MSCs may be the possible mechanism in CIA.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2009年第6期368-371,I0001,共5页
Chinese Journal of Rheumatology
基金
国家自然科学基金（30772014）
江苏省科教兴卫工程重点人才基金（RC2007002）
