芹菜素通过减轻髓核细胞炎症和基质降解来缓解体内椎间盘退变。
Acacetin Alleviates Inflammation and Matrix Degradation in Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration in vivo.
机构信息
Department of Orthopaedic Surgery, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, People's Republic of China.
Department of Orthopaedic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People's Republic of China.
出版信息
Drug Des Devel Ther. 2020 Nov 10;14:4801-4813. doi: 10.2147/DDDT.S274812. eCollection 2020.
PURPOSE
Intervertebral disc degeneration (IDD) is one of the most prevalent musculoskeletal disorders. The nucleus pulposus is the major component of the intervertebral disc, and nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the intervertebral disc. Reactive oxygen species (ROS) generation, inflammation and extracellular matrix degradation in NPCs contribute to the degeneration of intervertebral discs. Acacetin is a drug that exerts antioxidant and anti-inflammatory effects on many types of cells. However, whether acacetin can relieve the degeneration of NPCs remains unknown.
METHODS
NPCs were extracted from rat intervertebral discs. The NPCs were treated with tert-butyl peroxide (TBHP) to simulate a high-ROS environment, and acacetin was subsequently added. The contents of ROS, inflammatory mediators (COX-2, iNOS) and extracellular matrix components (aggrecan, collagen II, MMP13, MMP9, MMP3) were measured. Components of related signaling pathways (Nrf2, MAPK) were also evaluated. To determine the effect of acacetin in vivo, we simulated disc degeneration via needle puncture. Acacetin was then applied intraperitoneally, and the degenerative status was evaluated using MRI and histopathological analysis.
RESULTS
In vitro, acacetin alleviated TBHP-induced ROS generation and upregulated the expression of antioxidant proteins, including HO-1, NQO1, and SOD. In addition, acacetin relieved the TBHP-induced generation of inflammatory mediators (COX-2, iNOS) and degradation of the extracellular matrix (aggrecan, collagen II, MMP13, MMP9, and MMP3). Acacetin exerted its effect by activating the Nrf2 pathway and inhibiting p38, JNK and ERK1/2 phosphorylation. In vivo, acacetin ameliorated puncture-induced disc degeneration in a rat tail model, which was evaluated using MRI and histopathological analysis.
CONCLUSION
Acacetin alleviated IDD in vitro and in vivo and may have the potential to be developed as an effective treatment for IDD.
目的
椎间盘退变（IDD）是最常见的肌肉骨骼疾病之一。髓核是椎间盘的主要组成部分，髓核细胞（NPC）在椎间盘的正常功能中起着重要作用。NPC 中活性氧（ROS）的产生、炎症和细胞外基质降解导致椎间盘退变。阿克替宁是一种对多种类型的细胞具有抗氧化和抗炎作用的药物。然而，阿克替宁是否能缓解 NPC 的退变尚不清楚。
方法
从大鼠椎间盘提取 NPC。用叔丁基过氧化物（TBHP）处理 NPC 以模拟高 ROS 环境，然后加入阿克替宁。测量 ROS、炎症介质（COX-2、iNOS）和细胞外基质成分（聚集蛋白聚糖、胶原 II、MMP13、MMP9、MMP3）的含量。还评估了相关信号通路（Nrf2、MAPK）的组成部分。为了确定阿克替宁在体内的作用，我们通过针刺模拟椎间盘退变。然后腹腔内给予阿克替宁，并通过 MRI 和组织病理学分析评估退变状态。
结果
在体外，阿克替宁减轻了 TBHP 诱导的 ROS 生成，并上调了抗氧化蛋白的表达，包括 HO-1、NQO1 和 SOD。此外，阿克替宁减轻了 TBHP 诱导的炎症介质（COX-2、iNOS）和细胞外基质（聚集蛋白聚糖、胶原 II、MMP13、MMP9 和 MMP3）的降解。阿克替宁通过激活 Nrf2 通路和抑制 p38、JNK 和 ERK1/2 磷酸化发挥作用。在体内，阿克替宁改善了大鼠尾模型中针刺诱导的椎间盘退变，通过 MRI 和组织病理学分析进行评估。
结论
阿克替宁在体外和体内减轻了 IDD，并可能具有开发为 IDD 有效治疗方法的潜力。
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