ABSTRACT

Aim: Maresin-1 is a metabolite of docosahexaenoic acid (DHA) that has potential anti-inflammatory effects. To explore whether maresin-1 changes and has a therapeutic effect in osteoarthritis (OA) model rats undergoing treadmill exercise, we examined endogenous maresin-1 in a single-session treadmill experiment and OA model rats were treated with maresin-1, moreover, we examined the effects of maresin-1 on IL-1β induced rat fibroblast-like synoviocytes (FLSs) and possible mechanisms.

Methods: In single-session treadmill experiment, 48 rats were randomly divided into 3 groups and performed three different intensities of exercise (15.2 m/min, 0°; 19.3 m/min, 5°; 26.8 m/min, 10°) for 60 min. Intra-articular lavage fluid (IALF) samples were harvested after 0, 2, and 4 h from each group (n = 4) and maresin-1 levels were evaluated by ELISA. Another 30 rats were treated with monosodium iodoacetate (MIA) to induce osteoarthritis and exogenous maresin-1 (MaR-1) and were divided into three groups (n = 10, OA: MIA, OAM: MIA+MaR1, and CG: control group). The level of injury was evaluated by OARSI and Mankin scores, and the levels of type II collagen and MMP13 were evaluated by immunohistochemistry. FLSs were obtained from the knee joint of SD rats, and the expression of MMP13 and activation of the PI3k/Akt and NF-κB p65 pathways in IL-1β-induced FLSs were evaluated by western blotting.

Results: Maresin-1 levels were increased in IALF at 4 h after exercise, and type II collagen increased in cartilage and MMP13 decreased in the synovium after treatment with maresin-1 in MIA-induced osteoarthritis. The results of vitro experiment showed decreased MMP13, activation of the PI3k/Akt pathway, and suppression of the NF-κB p65 pathway upon treatment with maresin-1 in IL-1β-induced FLSs.

Conclusions: The changes in maresin-1 in IALF, as seen in our single-section treadmill exercise, provides an explanation for the therapeutic effect of appropriate-strength treadmill exercise on osteoarthritis, and our experiments confirmed the therapeutic effect of maresin-1 both in vivo and in vitro.

摘要

目的：Maresin-1 是二十二碳六烯酸 (DHA) 的代谢物，具有潜在的抗炎作用。为了探讨 maresin-1 对骨关节炎 (OA) 模型大鼠在跑步机运动中是否发生变化并具有治疗作用，我们在单次跑步机实验中检测了内源性 maresin-1，并对 OA 模型大鼠进行了 maresin-1 治疗，此外，我们检查了 maresin-1 对 IL-1β 诱导的大鼠成纤维细胞样滑膜细胞 (FLS) 的影响和可能的机制。

方法：单次跑步机实验中，48只大鼠随机分为3组，进行3种不同强度的运动（15.2 m/min，0°；19.3 m/min，5°；26.8 m/min，10°）60分钟。在每组 (n = 4) 0、2 和 4 小时后收集关节内灌洗液 (IALF) 样品，并通过 ELISA 评估 maresin-1 水平。另外 30 只大鼠用碘乙酸单钠 (MIA) 诱导骨关节炎和外源性 maresin-1 (MaR-1) 并分为三组 (n = 10, OA: MIA, OAM: MIA+MaR1, CG: 对照组）。采用OARSI和Mankin评分评价损伤程度，免疫组化评价Ⅱ型胶原和MMP13水平。FLSs取自SD大鼠的膝关节，

结果：运动后 4 小时 IALF 中 Maresin-1 水平升高，在 MIA 诱导的骨关节炎中用 maresin-1 治疗后，软骨中 II 型胶原蛋白增加，滑膜中 MMP13 降低。体外实验结果显示，在 IL-1β 诱导的 FLSs 中，用 maresin-1 处理后 MMP13 降低、PI3k/Akt 通路激活和 NF-κB p65 通路抑制。

结论： IALF 中 maresin-1 的变化，正如我们的单节跑步机运动所见，为适当强度的跑步机运动对骨关节炎的治疗效果提供了解释，我们的实验证实了 maresin-1 的治疗效果体内和体外。