脐带间充质干细胞移植治疗大鼠胶原诱导关节炎模型的疗效观察

Effect observation of umbilical cord-derived mesenchymal stem cells transplantation on treatment of collagen-induced arthritis rats

目的探讨脐带间充质干细胞(UCMSCs)移植治疗大鼠胶原诱导关节炎(CIA)模型的疗效。方法 40只造模成功的Wistar大鼠随机分为MSCs移植治疗组(MSC组,n=20)、细胞对照组(FLS组,n=10)、疾病对照组(CIA组,n=10),10只正常的Wistar大鼠作为正常对照组。采用AI评分来评价CIA大鼠关节肿胀程度。第17天予MSC组CIA大鼠尾静脉注射1×106UCMSCs,FLSs组CIA大鼠尾静脉注射等量成纤维样滑膜细胞。第42天处死所有大鼠,外周血分离血清,踝关节HE染色。ELISA法检测血清中TNF-α、TGF-β、IL-1β、IL-6水平。踝关节病理评价关节间隙狭窄程度。结果 MSC组大鼠关节AI低于FLS组和CIA组(P<0.05);HE染色示CIA大鼠造模后踝关节出现炎性细胞浸润及关节腔狭窄,但MSC治疗组关节间隙明显好于CIA组和FLS组;CIA组和FLS组TNF-α、IL-1β、IL-6水平均高于正常对照组,MSC治疗组TNF-α、IL-1β、IL-6水平较CIA组和FLS组均有显著下降(P<0.05);TGF-β在对照组与CIA组间差异无统计学意义,但输注MSC后TGF-β得到上调(P<0.01)。结论 UCMSCs移植能通过抑制炎性细胞因子TNF-α、IL-1β、IL-6,上调抑炎细胞因子TGF-β来减轻CIA大鼠关节炎症和软骨破坏。

Objective To investigate the effect of umbilical cord-derived mesenchymal stem cells（UCMSCs） transplantation on treatment of collagen-induced arthritis（CIA） rats. Methods Forty CIA model of Wistar rats were randomly divided into MSCs transplantation group（MSC group,n= 20）,cells control group（FLS group,n = 10） and disease control group（CIA group,n = 10）,and10 normal Wistar rats were selected as normal control group. AI score was used to evaluate the degree of joint swelling in CIA rats. 1 × 10^6 UCMSCs or FLSs was given through intravenous injection from tail veil on the 17 th day in the MSC group and the FLS group. On the 42 nd day,rats were sacrificed and sera were got for detecting TNF-α,TGF-β,IL-1β and IL-6. Ankle joint was got for pathological evaluation of the narrowing degree. Results Arthritis scores of the MSC group were significantly lower than those of the CIA group and the FLS group（P〈 0. 05）. HE staining showed that inflammatory cells infiltration and arthrostenosis were amiliorated by MSC. High serum levels of TNF-α,IL-1β and IL-6 were down-regulated through UCMSCs transplantation（P〈 0. 05）. There was no significant difference of TGF-β between the control group and the CIA group,but up-regulated after the infusion of UCMSCs（P〈 0. 01）. Conclusion UCMSCs transplantation can alleviate arthritis and cartilage damage in CIA rats by down regulating inflammatory cytokines of TNF-α,IL-1β,IL-6 and up regulating TGF-β.