骨关节炎滑膜细胞分泌肿瘤坏死因子的生物学特征研究

Biological Features of Osteoarthritic Synoviocytes in Synthesizing and Secreting Tumor Necrosis Factor-a

目的探讨滑液中肿瘤坏死因子（ｔｕｍｏｒ ｎｅｃｒｏｓｉｓ ｆａｃｔｏｒ－ ａ， ＴＮＦ－ ａ）生物活性及滑膜细胞分泌ＴＮＦ－α能力的变化在骨关节炎（ｏｓｔｅｏａｒｔｈｒｉｔｉｓ，ＯＡ）致病机制中的作用。方法应用ＴＮＦ－ａ对Ｌ９２９细胞杀伤作用的比色法，检测并比较分析ＯＡ与不同年龄、不同形式关节内创伤时滑液和血清中ＴＮＦ－α生物活性，以及培养的ＯＡ、急性关节内创伤和正常滑膜细胞自分泌及诱生性ＴＮＦ－α生物活性的变化。结果ＯＡ的滑液和血清中、老年慢性关节内创伤血清中、急性关节内创伤滑液中含较高水平的ＴＮＦ－α。培养的 ＯＡ和急性关节内创伤滑膜细胞可自分泌ＴＮＦ－α，对细菌脂多糖（ｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅ，ＬＰＳ）刺激的反应性和敏感性较正常滑膜细胞增强，分泌ＴＮＦ－ａ的能力提高，诱生性ＴＮＦ－ａ的量与ＬＰＳ呈时间一效应和剂量一效应的依赖关系。结论ＯＡ滑液中高水平的ＴＮＦ—ａ与其血清中异常升高的ＴＮＦ－ａ和滑膜细胞变性有关，而急性关节内创伤的滑液中高水平的ＴＮＦ－ａ可来源于变性的滑膜细胞。滑液中ＴＮＦ—ａ的异常升高和滑膜细胞变性，是ＯＡ发生、发展的重要介导因素。

Objective TO investigate the changes of biological features of synoviocytes in synthesizing and secreting tumor necrosis factor -- a (TNF -- a) in the pathogenesis of osteoarthritis(OA). Methods Synovial fluid(SF) and serum were collected from patients with OA and from patients with chronic and acute joint trauma and normal joints. The synoviocytes were isolated from these specimens alld cultured. The bioactivity of TNF -- a in SF, serum and that produced by the synoviocytes were detected with method of L 929 cells killing test. Results The bioactivity of TNF -- ac both in SF and serum were higher in patients with OA, and the bioactivity of TNF -- a were higher in serum in patients with chronic traumatic joint or in SF in patients with acute traumatic joint. The level of TNF -- a spontaneously produced by the synoviocytes in OA and in acute traumatic joint and the sensibility of these cells to LPS -- induced TNF -- a secretion were also higher. LPS in doses from I ig/Inl to 10 ig/ml and in phase from 4 to 48 hours stimulated dose-dependent and time-dependent increase of TNF -- a. Conclusion TNF -- a may originate from serum in aged people or from synoviocytes with abnormal function and is associated with destructive process in OA.