Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague–Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

骨关节炎 (OA) 迫切需要新的治疗策略。棕榈酰乙醇酰胺 (PEA) 是一种天然存在的脂肪酸酰胺，具有镇痛和抗炎作用。我们旨在检查其对 OA 的影响并阐明在碘乙酸单钠 (MIA) 诱导的 OA Sprague-Dawley 大鼠中作用的分子机制。实验动物分为正常对照组（注射生理盐水+磷酸盐缓冲液（PBS）处理，NOR），对照组（注射MIA+PBS处理，CON），50或100mg/kg体重（ BW)/天 PEA治疗组（注射MIA+用50或100mg PEA/kg BW/天，PEA50或PEA100治疗）和阳性对照组（注射MIA+用6mg双氯芬酸/kg BW治疗） /天，DiC）。血液参数、身体参数的变化，观察炎症介质和细胞因子的基因表达、膝关节厚度和关节组织。口服 PEA 对 BW、肝脏或肾脏没有不良影响。PEA 减少了 MIA 诱导的 OA 大鼠的膝关节肿胀和软骨退化。与 CON 组相比，PEA100 组的血清白三烯 B4、一氧化氮、肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-1β 和前列腺素 E2 水平显着降低。膝关节滑膜中的 mRNA 表达 与 CON 组相比，PEA100 组的前列腺素 E2 显着降低。膝关节滑膜中的 mRNA 表达 与 CON 组相比，PEA100 组的前列腺素 E2 显着降低。膝关节滑膜中的 mRNA 表达iNOS、5-Lox、Cox-2、Il-1β、Tnf-α和Mmp -2、-3、-9和-13随着 MIA 给药明显增加。同时， CON组Timp-1 mRNA表达明显下降，但PEA处理后上升至正常水平。因此，PEA 可以成为 OA 的有效治疗剂。