γ-谷维素通过阻断 IL-1β/NLRP3 炎性小体正循环缓解椎间盘退变发展。
Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1β/NLRP3 inflammasome positive cycle.
机构信息
Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.
Department of Orthopaedics Surgery, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
出版信息
Phytomedicine. 2022 Jul 20;102:154176. doi: 10.1016/j.phymed.2022.154176. Epub 2022 May 16.
BACKGROUND
Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown.
PURPOSE
This study aims to validate the role of Ory in IVDD and explore the potential mechanism.
STUDY DESIGN
Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory.
METHOD
The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels.
RESULTS
Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development.
CONCLUSION
Our results support the potential application of Ory as a therapeutic compound for IVDD.
背景
椎间盘退变（IVDD）是一种高发的肌肉骨骼疾病，其特征是存在与白细胞介素-1β/NLRP3 炎性小体正反馈环相关的局部炎症反应。米糠衍生的γ-谷维素（Ory）作为一种甾醇阿魏酸酯，因其强大的抗炎、降血糖和降血脂的健康作用而备受关注。作为一种自主神经紊乱的临床药物，Ory 在肌肉骨骼退行性疾病中的作用尚不清楚。
目的
本研究旨在验证 Ory 在 IVDD 中的作用，并探讨其潜在机制。
研究设计
建立体外和体内 IVDD 模型，以检测 Ory 的保护作用和分子机制。
方法
通过免疫印迹和免疫荧光等方法评估 Ory 对 IL-1β 刺激的髓核（NP）细胞的抗细胞外基质降解、抗氧化和抗 NLRP3 炎性小体激活作用。通过 MRI、S-O 染色和免疫组织化学，在影像学和组织学水平上评估 Ory 给药对针刺介导的大鼠 IVDD 的影响。
结果
Ory 处理抑制了 IL-1β 介导的 NP 细胞细胞外基质降解、氧化应激和 NLRP3 炎性小体激活。通过干扰 NF-κB 信号和 ROS 过度产生，Ory 打断了 IL-1β/NLRP3 炎性小体的正循环。体内实验表明，Ory 延缓了针刺介导的 IVDD 发展。
结论
我们的结果支持 Ory 作为 IVDD 治疗化合物的潜在应用。
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