滑膜细胞凋亡在佐剂性关节炎大鼠关节炎症中的作用.docVIP

滑膜细胞凋亡在佐剂性关节炎大鼠关节炎症中的作用 【摘要】 目的：探讨成纤维样滑膜细胞凋亡在佐剂性关节炎（AA）大鼠关节炎症中的作用。方法：采用大鼠尾部皮内注射完全福氏佐剂（CFA）建立 AA 模型，注射 CFA 后第 14 日起，每隔 7 d 记录关节炎指数（AI），并每隔 7 d 引颈处死 1 组大鼠，组织块培养法分离培养 AA 大鼠膝关节成纤维样滑膜细胞，流式细胞仪检测成纤维样滑膜细胞凋亡；分析成纤维样滑膜细胞凋亡的改变与 AI 的相关性。结果：AI 在疾病早期逐渐增加，后期明显下降。流式细胞分析显示随 AA 病程延长 S 期滑膜细胞比例逐渐增加。在 AA 早期成纤维样滑膜细胞凋亡明显抑制，后期则凋亡抑制逐渐减弱，凋亡抑制与 AI显著相关。结论：在 AA 发病机制中，成纤维样滑膜细胞凋亡抑制可能在急性滑膜炎中起有一定作用。 【关键词】 实验性关节炎；成纤维样滑膜细胞；凋亡 〔Abstract〕ObjectiveTo explore the effects of proliferation and apoptosis of fibroblast-like synoviocyte on articular inflammation in adjuvant arthritis(AA). Methods 0.1 mL of the complete Freud’s adjuvant (CFA) was subcutaneously injected into the tail of Wistar rat. 14 days after CFA injection, Arthritis index (AI) was evaluated every 7 days and a group of rats (6 rats) were executed every 7 days. Fibroblast-like synoviocyte was cultured in vitro. The amount of apoptotic cells and cells in S-phase was measured by flow cytometry. The correlation of fibroblast-like synoviocyte apoptosis and AI was analyzed. Results AI was increased in the early course of AA, but decreased in the later course. Flow cytometry demonstrated the amount of cells in S-phase increased with the course of AA progressed. The increase of S-phase cells positively correlated to the increase of RI. Apoptosis of fibroblast-like synoviocyte in the early course of AA was significantly inhibited, but the inhibition attenuated in the later course. Apoptosis inhibition was positively correlated to the increase of AI.ConclusionIn the pathogenesis of AA, the inhibition of fibroblast-like synoviocyte apoptosis may take a role in acute synovial inflammtion. 〔Key Words〕 Experimental; Arthritis; Fibroblast-like synoviocytes; Apoptosis 类风湿关节炎（rheumatoid arthritis, RA）是一种常见的严重危害人类身心健康的多因素导致的系统性自身免疫性疾病，其病理机制的关键在于关节反复的炎症、滑膜细胞“肿瘤样”增生以及由此引起的软骨和骨质破坏，其中成纤维样滑膜细胞是关节滑膜细胞中主要的一种[1]。研究显示引起 RA 关节滑膜组织过度增生的基本原因可能是由于滑膜细胞凋亡机制障碍所导致的滑膜组织内细胞的增殖和死亡之间的平衡失调而引起[2]。本研究拟观察大鼠佐剂性关节炎（adjuvant arthritis, AA）不同时间点关节成纤维样滑膜细胞凋亡与炎症指数（AI）的关系，以进一步明确滑膜