Nitric oxide: An important articular free radical
Nitric oxide: An important articular free radical
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DOI：
10.2106/00004623-199602000-00014
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发表时间：
1996-02-01
影响因子：
5.3
通讯作者：
Hannafin, JA
中科院分区：
文献类型：
--
作者：
Murrell, GAC;Dolan, MM;Hannafin, JA
一氧化氮是一种由一氧化氮合酶家族合成的小分子，在类风湿性关节炎和骨关节病中过量产生。本研究的目的是阐明关节组织中一氧化氮的潜在来源，并确定是否可以通过地塞米松或甲氨蝶呤抑制一氧化氮合酶的产生，这两种药物可以抑制其他形式的诱导型一氧化氮合酶。它是一氧化氮合酶的辅助因子。在内毒素、白细胞介素-1 β或肿瘤坏死因子- α刺激下，人、牛软骨外植体和培养的软骨细胞释放出大量亚硝酸盐，这是一氧化氮的稳定终产物。亚硝酸盐的产生具有时间依赖性和内毒素、白细胞介素-1 β和肿瘤坏死因子- α的剂量依赖性，并被一氧化氮合酶抑制剂N - omega-硝基- l -精氨酸甲酯和氨基胍抑制。牛软骨细胞诱导型一氧化氮合酶具有钙依赖性，可被高浓度甲氨蝶呤或地塞米松抑制。新鲜的牛关节滑膜组织外植体释放亚硝酸盐，该亚硝酸盐被No-硝基- l -精氨酸甲酯抑制，但内毒素、白细胞介素-1 β或肿瘤坏死因子α不能增强其释放。来源于人类滑膜组织或肩囊的外植体或细胞，或来源于犬前交叉韧带、后交叉韧带、内侧副韧带、外侧副韧带或髌骨韧带的外植体或细胞，都不能形成或诱导产生亚硝酸盐。综上所述，这些结果表明，软骨细胞是关节炎症或感染期间诱导型一氧化氮合酶和一氧化氮的主要来源。临床意义：由于一氧化氮是一种自由基，其作用非常迅速、局部且具有潜在毒性，因此在感染或炎症期间诱导高水平的软骨细胞一氧化氮可能是某些炎性关节病中软骨损伤的部分原因。抑制一氧化氮合酶的药物，尤其是诱导型一氧化氮合酶的选择性抑制剂，可能为抑制软骨的破坏提供新的有用的手段。
Nitric oxide is a small molecule that is synthesized by a family of enzymes, the nitric oxide synthases, and is overproduced in rheumatoid arthritis and osteoarthrosis, The aim of this investigation was to elucidate the potential sources of nitric oxide in joint tissues and to determine if the production of nitric oxide could be inhibited by dexamethasone or methotrexate, two agents that inhibit other forms of inducible nitric oxide synthase, Methotrexate inhibits the synthesis of biopterin, which is a co-factor for nitric oxide synthase.Explants of human and bovine cartilage and cultured chondrocytes released large amounts of nitrite, the stable end product of nitric oxide, when stimulated with endotoxin, interleukin-1 beta, or tumor necrosis factor-alpha, The production of nitrite was time-dependent and endotoxin, interleukin-1 beta, and tumor necrosis factor-alpha dose-dependent and was inhibited by the nitric-oxide-synthase inhibitors N omega-nitro-L-arginine methyl ester and aminoguanidine, The inducible nitric oxide synthase in bovine chondrocytes was calcium-dependent and was inhibited by high concentrations of methotrexate or dexamethasone. No constitutive nitric-oxide-synthase activity and little or no inducible nitric-oxide-synthase activity were demonstrable in explants or cell cultures derived from menisci, Fresh explants of bovine articular synovial tissue constitutively released nitrite that was inhibited by No-nitro-L-arginine methyl ester, but the release could not be enhanced by endotoxin, interleukin-1 beta, or tumor necrosis factor-alpha, There was no constitutive or inducible production of nitrite by explants or cells derived from the synovial tissue or shoulder capsule of a human or by explants or cells derived from canine anterior cruciate, posterior cruciate, medial collateral, lateral collateral, or patellar ligaments, Taken together, these results indicate that chondrocytes represent the major source of inducible nitric oxide synthase and nitric oxide during inflammation or infection of a joint.CLINICAL RELEVANCE: Since nitric oxide is a free radical, its effects are extremely rapid, local, and potentially toxic, Induction of high levels of chondrocytic nitric oxide during infection or inflammation may be responsible in part for the damage to cartilage that occurs in some inflammatory arthropathies. Agents that inhibit nitric oxide synthase, especially selective inhibitors of the inducible form of nitric oxide synthase, may offer new and useful means of inhibiting the destruction of cartilage.