阻断内甲蛋白受体可以减轻SARS-CoV-2引起的关节炎
Man Ting Au1, Junguo Ni1, Kaiming Tang2
1Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.
Nature microbiology
|September 11, 2024
概括
后COVID-19关节疼痛和骨关节炎涉及关节软骨损伤. 用macitentan准内分泌素受体信号传递可能通过减轻关节损伤和疼痛来治疗这些疾病.
科学领域:
- 整形外科 整形外科 整形外科
- 病毒学 病毒学
- 药理学 药理学是指药理学的学科.
背景情况:
- 关节疼痛和骨关节炎是2019年冠状病毒疾病 (COVID-19) 的潜在后果.
- 在SARS-CoV-2感染后关节软骨损伤的具体机制在很大程度上是未知的.
研究的目的:
- 在SARS-CoV-2感染后的患者和仓鼠模型中调查膝关节关节损伤.
- 探索内甲蛋白-1信号在COVID后关节病理学中的作用.
- 为了评估内甲素受体阻断对COVID后关节炎的治疗潜力.
主要方法:
- 使用感染SARS-CoV-2变种 (野生型,三角形,欧米克朗) 的金色叙利亚仓鼠模型进行体内研究.
- 关节组织的组织学分析以评估损伤,包括骨质细胞激活和冠状细胞变化.
- 在急性和后急性感染阶段使用内甲素受体对抗剂macitentan的药理干预.
主要成果:
- SARS-CoV-2 感染导致膝关节快速受伤,骨质突节结处有囊性病变,在仓鼠中重现.
- 激活的内甲素-1信号增加了血管透性,允许病毒尖端蛋白进入亚冠状骨,导致骨质细胞激活和冠状细胞损失.
- 马西坦治疗缓解了囊性病变,保存了冠状细胞,缓解了冠状细胞衰老,恢复了下冠状骨,并减少了关节疼痛.
结论:
- SARS-CoV-2 感染会引起由内甲蛋白-1 信号传递介导的显著关节损伤.
- 用macitentan阻断内分泌素受体显示出治疗潜力,用于管理COVID-19后的关节疼痛和骨关节炎.
- 准内啡林信号提供了一个新的治疗策略,用于COVID后关节炎.
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