Autophagy:骨关节炎无创治疗新进展:低强度脉冲超声缓解骨关节滑膜炎和自噬相关

2019-09-28 佚名 中国生物技术网

骨关节炎(osteoarthritis,OA)是最常见的骨关节相关疾病,造成的关节疼痛和功能障碍给患者带来极大的痛苦和经济负担(1)。目前治疗骨关节炎的方法主要包括药物,手术和物理治疗等。骨关节炎的重要病理特征是以巨噬细胞浸润为主的慢性、低度炎症滑膜炎症反应,滑膜炎与骨关节炎的病理发展和临床症状密切相关。靶向滑膜炎是防治骨关节炎和缓解骨关节炎症状的重要策略。

骨关节炎(osteoarthritis,OA)是最常见的骨关节相关疾病,造成的关节疼痛和功能障碍给患者带来极大的痛苦和经济负担(1)。目前治疗骨关节炎的方法主要包括药物,手术和物理治疗等。骨关节炎的重要病理特征是以巨噬细胞浸润为主的慢性、低度炎症滑膜炎症反应,滑膜炎与骨关节炎的病理发展和临床症状密切相关。靶向滑膜炎是防治骨关节炎和缓解骨关节炎症状的重要策略。

超声在临床上是一种常用的物理诊断和治疗手段。低强度脉冲超声(low-intensity pulsed ultrasound,LIPUS)是一种以脉冲形式发出的超声波物理因子,其强度一般小于100 mW/cm2。LIPUS也是一项安全无创的康复物理治疗手段,临床上LIPUS主要用于新鲜骨折的保守治疗和骨折不愈治疗等。目前有临床研究表明LIPUS可以缓解OA患者的疼痛,改善其日常生活能力(2),LIPUS的生物学效应主要通过机械振动效应实现,但相关深入的机制有待进一步解析。

2019年9月22日,陆军军医大学(原第三军医大学)陈林教授团队在Autophagy(最新影响因子11.059)杂志上在线发表题为“SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1βand contributes to LIPUS-mediated anti-inflammatory effect”的文章,研究结果表明:低强度脉冲超声可以抑制炎症反应,包括骨关节滑膜炎和脂多糖诱导的皮下炎症,能改善骨关节炎小鼠的疼痛步态并抑制关节滑膜炎病理变化,并首次发现LIPUS的抗炎效应和其促进巨噬细胞的自噬水平相关,LIPUS可以通过促进自噬来抑制炎症小体对白介素1β的加工剪切。并且首次证实在巨噬细胞中,糖酵解的关键酶PKM2和自噬的底物蛋白SQSTM/p62存在相互作用,而LIPUS能加速该复合物的形成,促进PKM2的降解,从而降低滑膜的炎症水平。该研究利用多种模型和技术手段从全新的角度解析了LIPUS缓解骨关节炎症状的机制,为未来研究无创的康复物理因子治疗提供了新思路。

物理因子治疗一直受到临床的欢迎,具有无创,低成本,便利,非侵袭性和安全等优势,对于骨关节炎的防治具有独特的治疗优势,但是由于物理因子对人体的具体生物学机制尚不完全清楚,物理因子的适应症也不是很明确,因此,明确物理因子在不同疾病,不同组织中的疗效以及研究其机制,优化康复因子在不同的条件下的治疗方案是未来的研究方向。

据悉,该研究的第一完成单位为陆军军医大学大坪医院野战外科研究所创伤实验室,通讯作者包括倪振洪博士后和陈林教授,第一作者为张斌(陈林教授2016级硕士生)。

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    2019-12-11 lisa438
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    2019-09-30 lmm397
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    2019-09-30 pcw106

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