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佩拉戈尼丁通过抑制NF-κB通路来改善骨关节炎的炎症反应和软骨退化

Zhi Zeng¹, Hao Li², Chong Luo²

¹Department of Orthopedics, The 908th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Nanchang, Jiangxi, 330002, China; Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.

Archives of biochemistry and biophysics

|June 14, 2023

概括

佩拉戈尼丁 (PG) 通过抑制NF-κB通路来减少骨关节炎 (OA) 中的炎症和软骨损伤. 这种安索亚宁衍生物在细胞培养和小鼠模型中都表现出保护作用,为OA治疗提供了潜力.

科学领域:

生物化学生物化学
药理学药理学是指药理学的学科.
免疫学免疫学免疫学

背景情况:

骨关节炎 (OA) 是一种退行性关节疾病,其特征是软骨的分解和炎症.
佩拉戈尼丁 (PG) 是一种安托西亚宁衍生物,具有已知的抗氧化和抗炎性质.
需要进一步研究PG在缓解骨关节炎进展方面的治疗潜力.

研究的目的:

评估佩拉戈尼丁 (PG) 对骨关节炎 (OA) 进展的保护作用.
阐明PG对抗关节炎相关的炎症和软骨退行的潜在机制.

主要方法:

建立了一个OA小鼠模型,使用中介半月 (DMM) 手术的不稳定.
初级冠状细胞被隔离并用IL-1β刺激,以模仿体外OA条件.
给OA小鼠和IL-1β刺激的红细胞;各种测试评估了细胞和组织的变化,包括基因/蛋白质表达和组织染色.

主要成果:

PG治疗 (10-40μM) 没有表现出软骨细胞中的细胞毒性,并且显著减少了促炎媒介 (IL-6,TNF-α,COX-2,iNOS).
通过保护原II并减少ADAMTS5和MMP13的表达,PG抑制了IL-1β诱导的细胞外基质 (ECM) 代谢.
在肌肉细胞中,PG抑制了NF-κB通路激活 (p-p65过度表达和核转位),改善了软骨损伤,降低了OARSI得分,并在DMM诱导的OA小鼠中调节了ECM标记表达.

结论:

佩拉戈尼丁 (PG) 有效地改善了骨关节炎的炎症反应和软骨退化.
PG通过抑制NF-κB信号通路来发挥其保护作用.
PG显示出作为抑制骨关节炎进展的治疗剂的显著潜力.

关键词:

软骨的退化软骨的退化炎症反应是一种炎症反应.通过NF-κB路径.骨关节炎是一种骨关节炎.佩拉戈尼尼迪尼是什么?佩拉戈尼迪尼是什么?

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