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臭氧治疗(O-O)通过抑制氧化应激和阻断 PI3K/Akt/NF-κB 信号通路来缓解早期椎间盘退变的进展。

Ozone therapy (O-O) alleviates the progression of early intervertebral disc degeneration via the inhibition of oxidative stress and the interception of the PI3K/Akt/NF-κB signaling pathway.

机构信息

Cell Therapy and Experimental Surgery of Musculoskeletal System LR18SP11 Lab, Faculty of Medicine, Sfax, Tunisia.

Cell Therapy and Experimental Surgery of Musculoskeletal System LR18SP11 Lab, Faculty of Medicine, Sfax, Tunisia; Department of Orthopedics and Traumatology, CHU Habib Bourguiba, Sfax, Tunisia.

出版信息

Int Immunopharmacol. 2024 Mar 10;129:111596. doi: 10.1016/j.intimp.2024.111596. Epub 2024 Feb 1.

Abstract

Intervertebral disc degeneration (IDD) stands for the most frequent cause of low back pain. Finding a cure for this disease is an important challenge as current conservative treatments and surgical interventions fail to bring a solution to this disease. Ozone therapy (O-O) has yielded outstanding outcomes in intervertebral disc pathology. The ozone's efficacy in the treatment of IDD remains unconfirmed. This study aimed to assess the effectiveness of intradiscal ozone injection on IDD induced in a rat. Effects of ozone therapy on the viability of nucleus pulposus cells were evaluated by CCK-8 assays. Macrophage immunoreactivity was detected by immunohistochemical, the expression of collagen type II was evaluated by western blot, and measurement of oxidative stress parameters was realized. Molecular docking studies were carried out in order to predict the interaction formed between O and the target enzymes, on the one hand, O with PI3K and, on the other hand, O with COX-2. IRM, X-ray, hematoxylin-eosin, and bleu alcian staining were realized to assess the therapeutic impacts of ozone in the puncture-induced rat model of IDD. In vivo, O ameliorated the IDD in the early stage of this disease. It was also displayed in molecular docking that O might bind to PI3K to suppress the PI3K/Akt/NF-κB signaling pathway. This study's results show that the O should be administered at the low grade of IDD and at an early stage because it cannot restore the advanced inflammatory alteration of the IVD. Our results corroborated also that O inhibits the progression of IDD via the PI3K/Akt/NF-κB signaling pathway, which supports O as an effective therapeutic option for treating IDD.

摘要

椎间盘退行性变(IDD)是引起下腰痛的最常见原因。找到治疗这种疾病的方法是一个重要的挑战,因为目前的保守治疗和手术干预都不能解决这种疾病。臭氧治疗(O-O)在椎间盘病理学方面取得了优异的效果。臭氧治疗 IDD 的疗效尚未得到证实。本研究旨在评估椎间盘内臭氧注射对大鼠诱导的 IDD 的疗效。通过 CCK-8 测定评估臭氧治疗对髓核细胞活力的影响。通过免疫组织化学检测巨噬细胞免疫反应,通过 Western blot 评估 II 型胶原的表达,并测量氧化应激参数。进行分子对接研究,以预测 O 与靶酶之间形成的相互作用,一方面是 O 与 PI3K,另一方面是 O 与 COX-2。进行 IRM、X 射线、苏木精-伊红和蓝染染色,以评估臭氧在穿刺诱导的大鼠 IDD 模型中的治疗作用。在体内,O 改善了这种疾病的早期 IDD。分子对接还表明,O 可能与 PI3K 结合,抑制 PI3K/Akt/NF-κB 信号通路。本研究结果表明,O 应该在 IDD 的低级别和早期阶段使用,因为它不能恢复 IVD 的晚期炎症改变。我们的结果还表明,O 通过 PI3K/Akt/NF-κB 信号通路抑制 IDD 的进展,这支持 O 作为治疗 IDD 的有效治疗选择。

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