Nitric oxide (NO) and reactive oxygen species (ROS) have been shown to be linked with numerous diseases, including osteoarthritis (OA). Our study aimed to examine the effect of simvastatin on NO‐ or ROS‐induced cyclooxygenase‐2 (COX‐2) expression in OA. Simvastatin has attracted considerable attention since the discovery of its pharmacological effects on different pathogenic processes, including inflammation. Here, we report that simvastatin treatment blocked sodium nitroprusside (SNP)‐ and interleukin 1 beta (IL‐1β)‐induced COX‐2 production. In addition, simvastatin attenuated SNP‐induced NO production and IL‐1β‐induced ROS generation. Treatment with simvastatin prevented SNP‐ and IL‐1β‐induced nuclear factor kappa B (NF‐κB) activity. Inhibiting NO production and ROS generation using N‐acetylcysteine (NAC) and NG‐monomethyl‐ l‐arginine ( l‐NMMA), respectively, accelerated the influence of simvastatin on NF‐κB activity. In addition, NAC blocked SNP and simvastatin‐mediated COX‐2 production and NF‐κB activity but did not alter IL‐1β and simvastatin‐mediated COX‐2 expression. l‐NMMA treatment also abolished IL‐1β‐mediated COX‐2 expression and NF‐κB activation, whereas SNP and simvastatin‐mediated COX‐2 expression were not altered compared with the levels in the SNP and simvastatin‐treated cells. Our findings suggested that simvastatin blocks COX‐2 expression by inhibiting SNP‐induced NO production and IL‐1β‐induced ROS generation by blocking the NF‐κB pathway.

中文翻译：

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辛伐他汀通过阻断兔关节软骨细胞中的核因子 κB 通路来消除一氧化氮和活性氧诱导的环氧合酶 2 表达。

一氧化氮 (NO) 和活性氧 (ROS) 已被证明与多种疾病有关，包括骨关节炎 (OA)。我们的研究旨在检查辛伐他汀对 OA 中 NO 或 ROS 诱导的环氧合酶 2 (COX-2) 表达的影响。自从发现辛伐他汀对不同致病过程（包括炎症）的药理作用以来，辛伐他汀引起了相当大的关注。在这里，我们报告辛伐他汀治疗阻断了硝普钠 (SNP) 和白介素 1 β (IL-1β) 诱导的 COX-2 产生。此外，辛伐他汀减弱了 SNP 诱导的 NO 产生和 IL-1β 诱导的 ROS 产生。辛伐他汀治疗阻止了 SNP 和 IL-1β 诱导的核因子 kappa B (NF-κB) 活性。使用N抑制 NO 产生和 ROS 生成-乙酰半胱氨酸（NAC）和NG-单甲基 -l-精氨酸（ l- NMMA）分别加速了辛伐他汀对NF-κB活性的影响。此外，NAC 阻断 SNP 和辛伐他汀介导的 COX-2 产生和 NF-κB 活性，但不改变 IL-1β 和辛伐他汀介导的 COX-2 表达。 l- NMMA 处理还消除了 IL-1β 介导的 COX-2 表达和 NF-κB 激活，而与 SNP 和辛伐他汀处理的细胞中的水平相比，SNP 和辛伐他汀介导的 COX-2 表达没有改变。我们的研究结果表明，辛伐他汀通过阻断 NF-κB 通路来抑制 SNP 诱导的 NO 产生和 IL-1β 诱导的 ROS 产生，从而阻断 COX-2 表达。