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目的研究类风湿关节炎(RA)成纤维样滑膜细胞(FLS)体外培养时的增生分化特点及细胞分化诱导剂全反式维甲酸(ATRA)、骨化三醇[1,25(OH)_2D_3]、地塞米松(DEX)对RA-FLS增殖分化的影响。方法关节镜、关节活检针取RA患者滑膜组织或抽取RA患者关节积液分离培养鉴定滑膜细胞,四甲基偶氮唑蓝(MTT)法和流式细胞仪法分别观察ATRA、骨化三醇和地塞米松对FLS细胞存活分数(SF)和细胞周期的影响。结果RA-FLS在体外无诱导剂作用时呈现良性增殖方式。ATRA、骨化三醇和地塞米松对FLS的细胞标记和免疫染色无明显影响。三种诱导剂对RA-FLS的SF值均有不同程度的抑制(P<0.05),其中地塞米松抑制作用最明显;骨化三醇和地塞米松对RA-FLS的SF抑制作用呈现剂量依赖性曲线(P<0.01)。三种诱导剂均促使RA-FLS细胞周期改变即凋亡峰出现、S期缩短。结论体外培养的RA-FLS生长特性为非恶性无限制增生。ATRA、骨化三醇和地塞米松抑制RA-FLS细胞增殖,促进细胞分化,诱导FLS凋亡,其中地塞米松抗增殖作用最明显;但未发现三者将FLS诱导分化为其他类型细胞。
Objective To study the proliferation and differentiation of rheumatoid arthritis (RA) fibroblast - like synoviocytes (FLS) in vitro and the effects of allogenic trans retinoic acid (ATRA), calcitriol [1,25 (OH) _2D_3], dexamethasone (DEX) on proliferation and differentiation of RA-FLS. Methods Arthroscopic and biopsy specimens were taken from the synovial tissue of patients with RA or from the synovial fluid of RA patients for synovial differentiation. MTT and flow cytometry were used to detect the expression of ATRA, Effects of triols and dexamethasone on survival score and cell cycle of FLS cells. Results RA-FLS showed a benign proliferation mode in vitro without inducing agents. ATRA, calcitriol, and dexamethasone had no significant effect on FLS cell labeling and immunostaining. The inhibitory effect of dexamethasone was the most significant (P <0.05). The inhibitory effect of calcitriol and dexamethasone on RA-FLS was dose-dependent Sex curve (P <0.01). Three kinds of inducing agents all promote the change of cell cycle of RA-FLS, ie, the peak of apoptosis occurs, S phase shortens. Conclusion The growth characteristics of RA-FLS cultured in vitro are non-malignant and unlimited proliferation. ATRA, calcitriol and dexamethasone could inhibit the proliferation of RA-FLS cells, promote cell differentiation and induce apoptosis of FLS. Among them, dexamethasone had the most obvious antiproliferative effect. However, it was not found that FLS induced differentiation into other cell types.