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马尿酸-1 通过激活 PI3K/AKT 通路和抑制 NF-κB 通路抑制骨关节炎大鼠模型滑膜成纤维细胞中 IL-1β诱导的 MMP-13 分泌。

Maresin-1 suppresses IL-1β-induced MMP-13 secretion by activating the PI3K/AKT pathway and inhibiting the NF-κB pathway in synovioblasts of an osteoarthritis rat model with treadmill exercise.

机构信息

Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Connect Tissue Res. 2021 Sep;62(5):508-518. doi: 10.1080/03008207.2020.1780218. Epub 2020 Jun 16.

DOI:10.1080/03008207.2020.1780218
PMID:32546009
Abstract

: 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.: 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.: 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.: 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

马雷斯汀-1 是二十二碳六烯酸(DHA)的一种代谢产物,具有潜在的抗炎作用。为了探讨马雷斯汀-1 在进行跑步机运动的骨关节炎(OA)模型大鼠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马雷斯汀-1,并用马雷斯汀-1 治疗 OA 模型大鼠,此外,我们还检测了马雷斯汀-1 对白细胞介素 1β诱导的大鼠成纤维样滑膜细胞(FLSs)的影响及其可能的机制。

在单次跑步机实验中,将 48 只大鼠随机分为 3 组,并进行 3 种不同强度的运动(15.2 m/min,0°;19.3 m/min,5°;26.8 m/min,10°),持续 60 min。从每组(n = 4)中采集 0、2 和 4 h 的关节内灌洗液(IALF)样本,并通过 ELISA 评估马雷斯汀-1 水平。另外 30 只大鼠用单碘乙酸(MIA)诱导骨关节炎,并给予外源性马雷斯汀-1(MaR-1),分为三组(n = 10,OA:MIA、OAM:MIA+MaR1 和 CG:对照组)。通过 OARSI 和 Mankin 评分评估损伤程度,通过免疫组织化学评估 II 型胶原和 MMP13 的水平。从 SD 大鼠膝关节中获得 FLSs,并通过 Western blot 评估 IL-1β诱导的 FLSs 中 MMP13 的表达和 PI3k/Akt 和 NF-κB p65 通路的激活。

运动后 4 h,IALF 中马雷斯汀-1 水平升高,MIA 诱导的骨关节炎大鼠给予马雷斯汀-1 治疗后软骨中 II 型胶原增加,滑膜中 MMP13 减少。体外实验结果表明,IL-1β诱导的 FLSs 中 MMP13 减少,PI3k/Akt 通路激活,NF-κB p65 通路受到抑制。

我们的单节跑步机运动实验观察到 IALF 中马雷斯汀-1 的变化,为适当强度跑步机运动对骨关节炎的治疗作用提供了解释,我们的实验在体内和体外均证实了马雷斯汀-1 的治疗作用。

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