异基因骨髓间充质干细胞移植对类风湿关节炎大鼠血清IL-1、TNF-α、TGF-β1表达的影响

Effect of Allo-Bone Marrow Mesenchymal Stem Cells Transplantation on Expression of IL-1,TNF-α,TGF-β of Rheumatoid Arthritis Rat

目的探讨异基因骨髓间充质干细胞(BM-MSCs)移植对类风湿关节炎(RA)动物模型(CIA大鼠)血清中白细胞介素-1(IL-1)、肿瘤坏死因子(TNF-α)和转化生长因子(TGF-β1)表达的影响。方法分别选取5只Wistar幼年大鼠和20只Wistar成年雌性大鼠。5只Wistar幼年大鼠用以提取BM-MSCs,20只Wistar成年雌性大鼠经CIA造模成功后随机分为BM-MSCs移植A组和空白对照B组。BM-MSCs分离、传代培养后,通过CIA大鼠尾静脉注射移植于A组动物,BM-MSC移植数目为1.0×107/kg(受者体重)。于移植4周后用ELISA方法分别检测2组动物血清中IL-1、TNF-α和TGF-β1的含量。结果经BM-MSCs移植治疗4周后,BM-MSCs移植组血清中IL-1和TNF-α的浓度明显低于空白对照组,与空白对照组比较差异有统计学意义(P<0.05)。同时血清TGF-β1的浓度明显高于空白对照组,与空白对照组比较差异有统计学意义(P<0.05)。结论异基因BM-MSCs移植可以影响CIA大鼠血清中IL-1、TNF-α和TGF-β1的表达,对类风湿关节炎的免疫紊乱有调节作用,有可能用于RA的治疗。

Objective To investigate the effect on expression of IL-1,TNF-α,TGF-β of CIA rat by allo-bone marrow mesenchymal stem cells transplantation.Methods 5 young Wistar rats and 20 adult female Wistar rats were selected,5 young Wistar rats were used for the extraction of mesenchymal stem cells and 20 adult female Wistar rats were divided into 2 groups：CIA rats group A（n = 10）and CIA rats group B（n = 10）.BM-MSCs of 5 young Wistar rats were isolated,cultured in vitro routinely and the fourth passages as taken for identification of specific surface antigens by flowcytometry.The model of CIA rats were established.1.0×107/kg BM-MSCs were implanted through tail vein to CIA rats group A.CIA rats,group B with 0.5 ml saline served as controls.At fourth week,Enzyme-linked immunosorbent assay（ELISA）examinations was used to detect the level of IL-1,TNF-α and TGF-β1 in serum of CIA rats.Results After four weeks of BM-MSCs transplantation,compared with group B,there were an decreased level of IL-1,TNF-α while an increased level of TGF-β1 in serum of CIA rats.The difference was statistically significant（P 0.05）.Conclusion The transplantation of allogeneic bone marrow mesenchymal stem cells have modulator effects on main cytokines of CIA rats in vivo.BM-MSCs could down regulates the level of IL-1 and TNF-α,but upregulates the level of TGF-β1.These immunomodulatory effects were not MHC restricted.That provided positive results for developing effective therapy for rheumatoid arthritis.