Shortly after joint remobilization, inflammation is induced in the joint and aggravates joint contracture via subsequent fibrosis. However, the mechanisms involved in remobilization-induced inflammation are not yet fully understood. We hypothesized that joint immobilization followed by remobilization induces hypoxia/reoxygenation, initiating inflammatory reactions through nitric oxide (NO) production via NO synthase 2 (NOS2). This study aimed to investigate whether: 1) administration of the NOS inhibitor L-NG-nitroarginine methyl ester (l-NAME) can attenuate remobilization-induced joint inflammation; and 2) hypoxia/reoxygenation is induced by joint immobilization and followed by remobilization. Unilateral knee joints of rats were immobilized using external fixators for three weeks. After removal of the fixation device, knees were allowed to move freely for one day (remobilization) with or without l-NAME administration. Without l-NAME administration, inflammatory reactions including joint swelling and inflammatory cell infiltration, edema, and upregulation of inflammatory mediator genes in the joint capsule were detected following upregulation of the NOS2 gene after remobilization. These remobilization-induced inflammatory reactions were partially attenuated by administration of l-NAME. Therefore, NOS2/NO elevation has potential as a novel treatment for remobilization-induced joint inflammation. Gene expression of the hypoxia marker hypoxia inducible factor-1α was upregulated after one day of remobilization, rather than after immobilization. These results suggest that upregulation of NOS2 by remobilization might be not due to hypoxia/reoxygenation.

中文翻译：

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一氧化氮合酶抑制剂L-NG-硝基精氨酸甲酯（L-NAME）减弱了运动诱发的关节发炎。

关节复位后不久，会在关节中引起炎症，并通过随后的纤维化加重关节挛缩。但是，尚未完全了解与动员诱导的炎症有关的机制。我们假设关节固定和随后的移动引起缺氧/复氧，通过一氧化氮（NO）通过一氧化氮合酶2（NOS2）产生炎症反应。这项研究旨在调查是否：1）服用NOS抑制剂L-NG-硝基精氨酸甲酯（l-NAME）可以减轻运动引起的关节炎症。2）缺氧/复氧由关节固定引起，然后再固定。使用外固定器将大鼠的单侧膝关节固定三周。卸下固定装置后，不论是否使用l-NAME，膝盖均可以自由移动一天（重新固定）。如果不使用l-NAME，则在动员后NOS2基因上调后，会检测到炎症反应，包括关节肿胀和炎症细胞浸润，水肿以及关节囊中炎症介质基因的上调。通过施用I-NAME，这些迁移诱导的炎症反应被部分减弱。因此，NOS2 / NO升高有潜力作为一种新的治疗方法，用于引起复员引起的关节发炎。低氧标志物低氧诱导因子-1α的基因表达在动员一天后而不是在动员后被上调。这些结果表明，通过上调NOS2的上调可能不是由于缺氧/复氧。