摘要
目的观察重组人内抑素对体外培养佐剂性关节炎大鼠滑膜细胞的增殖功能及产生细胞因子的影响,探讨其治疗佐剂性关节炎的作用机制。方法采用弗氏完全佐剂(CFA)诱导的佐剂性关节炎(AA)大鼠模型,用足容积法测量关节肿胀度;采用collagenasetypeⅡ消化法分离、培养滑膜细胞,MTT法检测重组人内抑素体内用药对滑膜细胞增殖的影响;放免法检测滑膜细胞上清液中IL-1β、TNF-α的含量。结果CFA致炎后d10,AA大鼠出现继发性炎症,此时皮下注射重组人内抑素(1·25,2·5,5mg·kg-1),连续7d,对照组于d10给予MTX(1·0mg·kg-1)。各剂量组能明显抑制AA大鼠的继发性足肿胀;重组人内抑素体内用药可明显减少AA大鼠滑膜细胞数量,抑制滑膜细胞的增殖,并呈剂量依赖关系;各剂量组均可明显抑制AA大鼠滑膜细胞产生过高的IL-1β和TNF-α。结论重组人内抑素抑制AA大鼠滑膜细胞过度的增殖及过高的细胞因子是其治疗AA的途径之一。
Aim To study the effect of recombinant human endostatin on proliferation and secretion of cytokines on synoviocyte from adjuvant arthritis （AA） rats in vivo, and to investigate the therapeutical mechanism of recombinant human endostatin on AA rats. Methods Adjuvant arthritis rat model was induced by a single intradermal injection of 100μl of CFA on d 0. The volume of rat hind paw was measured by means of Volume Meter. Synoviocytes from rat knees were excised and dispersed with sequential incubation of the collagenase type Ⅱ and trypsin. The proliferation of synoviocytes was measured by MTT; activities of IL-1β and TNF-α produced by synoviocytes were estimated with radioimmunoassay. Results The secondary inflammation of AA rats appeared on the d10 after injection of CFA.The therapeutic administration of recombinant human （ 1.25,2.5,5.0 mg · kg^- 1 ） were given from that time （d10）. Methotrexate（MTX, 1.0 mg · kg^-1） was given only once on d10. Recombinant human endostatin significantly reduced the secondary paw swelling and decreased the production of IL-1β and TNF-α from synovial supernatants. Recombinant human endostatin resulted in a dose-dependent reduction in the number of synoviocytes and inhibited the proliferation of synovial in vivo. Conclusion Recombinant human endostatin had an inhibitory effect on AA rats, which was related to its inhibition of proliferation and secretion of synoviocytes.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第1期59-63,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30572196)
关键词
重组人内抑素
佐剂性关节炎
滑膜细胞
增殖
细胞因子
recombinant human endostatin
adjuvant arthritis
synoviocytes
proliferation
cytokines
