肿瘤坏死因子-α对骨关节炎滑膜细胞增殖和RNA表达的影响  

Effects of tumor necrosis factor α on proliferation and RNA expression of human osteoarthritic synoviocytes

作　　者：邓廉夫[1] 柴本甫[1] 杨庆铭[1] 

机构地区：[1]上海第二医科大学瑞金医院伤骨科研究所

出　　处：《中国药理学通报》1998年第6期506-508,共3页Chinese Pharmacological Bulletin

摘　　要：目的探讨肿瘤坏死因子α（ＴＮＦα）对骨关节炎（ＯＡ）滑膜细胞增殖和ＲＮＡ表达的效应，以及ＯＡ治疗药物和生物制剂对这种作用的调节。方法分离、培养晚期ＯＡ滑膜细胞，采用ＭＴＴ比色法、放射自显影和液体闪烁技术，检测ＴＮＦα对滑膜细胞增殖及ＲＮＡ表达的影响，以及非甾体类和甾体类药物、生物制剂作用后的滑膜细胞对这种影响的反应性。结果ＴＮＦα可诱导滑膜成纤维细胞样细胞增殖，以ＴＮＦα浓度为５×１０５Ｕ·Ｌ－１作用２４ｈ最为明显（增殖率提高３７８％）；促进滑膜细胞摄取［３Ｈ］ＵＲ，使ＲＮＡ表达量增加。吲哚美辛作用后的滑膜细胞对ＴＮＦα的反应性未发生明显改变，而地塞米松和干扰素α高浓度时有拮抗ＴＮＦα促滑膜细胞增殖的作用。结论ＴＮＦα可促使ＯＡ滑膜细胞进一步变性，抗炎类药物和细胞因子对此无明显拮抗作用。AIM To investigate the effect of tumor necrosis factor α(TNF α) on proliferation and RNA expression of human osteoahritic synoviocytes, and for this effect, regulation of antiinflammatory drugs and cytokins. METHODS Human synoviocytes were isolated from tissues obtained from the hip and knee joints of osteoarthritis(OA) undergoing arthoplasty and cultured. Proliferantion of synoviocytes were determined using MTT colorimetric and radioautographic methods, respectively. Their RNA expression was determined by uridine incorporation. RESULTS At concentration from 5×10 4 to 5×10 6 U·L -1 ,TNF α stimulated proliferation and enhanced synthesis of RNA metabolism of OA synoviocytes. At 5×10 5 U·L -1 ,after 24 h incubation with OA synoviocytes, proliferative rate of synovial fibroblast cell increased 37 8%, and incorporation of uridine by synoviocytes reached maximum: 1 79×10 -8 %(μg·d -1 ). After the synoviocytes were incubated with various concentration of indomethacin(INDO), dexamethasone(DEX), EGF, IL 6 and IFN α,respectively, DEX and IFN α could antagonize TNF α induced proliferation of synoviocytes only when the drugs were used at levels above their therapeutic concentration. CONCLUSION TNF α can induce proliferation and RNA expression of OA synoviocytes. Antiinflammatory drugs and cytokins do not antagonize significantly this effect.

关 键 词：骨关节炎 滑膜细胞增殖 RNA 肿瘤坏死因子 

分 类 号：R684.3[医药卫生—骨科学] R971.1[医药卫生—外科学]