Menkes C J, Borderie D, Hernvann A, Ekindjian O
Service de Rhumatologie A, Hôpital Cochin, Paris.
Bull Acad Natl Med. 1999;183(4):785-95; discussion 795-6.
Nitric oxide (NOo) is an inorganic radical produced after the activation of a NO synthase involved in inflammatory and immune reactions. It can react with protein thiols to form nitrosothiols, a bioactive molecule or can generate in nitrite or nitrate. High concentrations of these metabolites have been found in sera and synovial fluids from patients with osteoarthritis, the higher synovial concentrations suggesting NOo intra-articular production. The aim of this study was to evaluate the capacity of osteoarthritic chondrocytes to produce bioactive NOo metabolites and to study the inhibitory effect of rhein, the active form of diacerhein. Chondrocytes were stimulated by interleukin-1 beta (1 ng/ml) during 24 hours in presence or absence of rhein (1.3 x 10-5, 6.5 x 10-6, 1.3 x 10-6 M) or diclofenac (10-5, 10-6 M). After 24 hours, nitrite and nitrosothiols were measured in the supernatants and nitrosothiols were also determined in cell lysats. After interleukin-1 beta stimulation chondrocytes produced great quantities of nitrosothiols and nitrite. This effect was inhibited in a dose dependent manner by rhein but not by diclofenac. In conclusion, chondrocytes produce high quantities of nitrosothiols after IL-1 beta stimulation and this effect is inhibited by rhein. This drug could be beneficial to prevent the destruction of osteoarthritic cartilage.
一氧化氮（NOₒ）是一种无机自由基，由参与炎症和免疫反应的一氧化氮合酶激活后产生。它可与蛋白质硫醇反应形成亚硝基硫醇，一种生物活性分子，或者生成亚硝酸盐或硝酸盐。在骨关节炎患者的血清和滑液中发现了高浓度的这些代谢产物，滑液中较高的浓度表明NOₒ是关节内产生的。本研究的目的是评估骨关节炎软骨细胞产生生物活性NOₒ代谢产物的能力，并研究双醋瑞因的活性形式大黄酸的抑制作用。在存在或不存在大黄酸（1.3×10⁻⁵、6.5×10⁻⁶、1.3×10⁻⁶M）或双氯芬酸（10⁻⁵、10⁻⁶M）的情况下，用白细胞介素-1β（1 ng/ml）刺激软骨细胞24小时。24小时后，测量上清液中的亚硝酸盐和亚硝基硫醇，并在细胞裂解物中也测定亚硝基硫醇。白细胞介素-1β刺激后，软骨细胞产生大量亚硝基硫醇和亚硝酸盐。这种作用被大黄酸以剂量依赖性方式抑制，但不被双氯芬酸抑制。总之，白细胞介素-1β刺激后软骨细胞产生大量亚硝基硫醇，这种作用被大黄酸抑制。这种药物可能有利于预防骨关节炎软骨的破坏。
