Netrin-1引导滑膜感觉神经萌发调控KOA外周痛敏及“温经活血”外治法干预效应的机制研究

关节疼痛与僵硬是膝骨关节炎（KOA）两大核心症状，痛觉敏化与滑膜纤维化是其缠绵难愈的重要原因。有证据显示，KOA滑膜纤维化所活化的血管内皮细胞具备分泌轴突导向因子Netrin-1的潜力，而Netrin-1能通过干预神经元表面DCC/UNC5受体调控感觉神经萌发和神经讯号传导；这一过程与KOA的外周痛敏密切相关。我们的前期研究已证实“温经活血”外治法不仅能够抑制KOA痛敏，同时也兼具抑制细胞焦亡而抗滑膜纤维化的作用。结合我们在预实验中对“KOA滑膜纤维化-Netrin-1-外周痛敏”病理环节的观察，有理由推断：KOA进程中滑膜纤维化环节的血管内皮细胞来源Netrin-1可通过调控导向性感觉神经萌发影响外周痛敏，而“温经活血”外治法的药效机制与其对此环节的干预有关。本课题将应用模式动物、电生理、分子生物学等方法验证科学假说，探明KOA症状间的病理联系及“温经活血”外治法的效应靶点。

Joint pain and stiffness are two major clinical symptoms of knee osteoarthritis (KOA), while hyperalgesia and synovial fibrosis are important reasons for their intractable pathologic process. Evidence suggests that vascular endothelial cells activated by synovial fibrosis of KOA have the potential to secrete axonal guidance factor Netrin-1, Netrin-1 regulate sensory nerve sprouting and then alter neuronal electrical conduction under the attraction/exclusion guiding with DCC/UNC5 receptors on the neuronal surface; and this process is closely related to peripheral hyperalgesia of KOA. Previous research of our team confirmed that "warming meridian and activating blood circulation" external treatment not only block nociceptors in synovial tissue to inhibit KOA hyperalgesia, but also inhibit cell pyroptosis to slow down the pathological progress of synovial fibrosis. Combining our observation on "KOA synovial fibrosis - Netrin-1- peripheral hyperalgesia" in the pre-experiment, it is reasonable to assume: Netrin-1 secreted by vascular endothelial cell under synovial fibrosis of KOA influence peripheral hyperalgesia by regulating sensory nerve sprouting in synovial tissue, and the pharmacodynamic mechanism of "warming meridian and activating blood circulation" external treatment is related to its intervention in this link. By means of transgenic animal, electrophysiology, molecular biology and other methods, the scientific hypothesis in this subject will be verified, and the pathological connection between KOA symptoms and the effect target of "warming meridian and activating blood circulation" external treatment will be investigated.