Department of Orthopedics, Lanzhou University Second Hospital, The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Gansu provincial hospital of TCM (The First Affiliated Hospital of Gansu University of Chinese Medicine), Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu 730000, China.
Department of Orthopedics, Lanzhou University Second Hospital, The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu 730000, China.
Int Immunopharmacol. 2024 Jun 15;134:112161. doi: 10.1016/j.intimp.2024.112161. Epub 2024 May 9.
Intervertebral disc degeneration (IVDD) is a leading cause of degenerative spinal disorders, involving complex biological processes. This study investigates the role of the kallikrein-kinin system (KKS) in IVDD, focusing on the protective effects of bradykinin (BK) on nucleus pulposus cells (NPCs) under oxidative stress. Clinical specimens were collected, and experiments were conducted using human and rat primary NPCs to elucidate BK's impact on tert-butyl hydroperoxide (TBHP)-induced oxidative stress and damage. The results demonstrate that BK significantly inhibits TBHP-induced NPC apoptosis and restores mitochondrial function. Further analysis reveals that this protective effect is mediated through the BK receptor 2 (B2R) and its downstream PI3K/AKT pathway. Additionally, BK/PLGA sustained-release microspheres were developed and validated in a rat model, highlighting their potential therapeutic efficacy for IVDD. Overall, this study sheds light on the crucial role of the KKS in IVDD pathogenesis and suggests targeting the B2R as a promising therapeutic strategy to delay IVDD progression and promote disc regeneration.
椎间盘退行性变（IVDD）是退行性脊柱疾病的主要原因，涉及复杂的生物学过程。本研究探讨激肽释放酶-激肽系统（KKS）在 IVDD 中的作用，重点研究缓激肽（BK）在氧化应激下对髓核细胞（NPC）的保护作用。本研究收集了临床标本，并使用人源和大鼠原代 NPC 进行实验，以阐明 BK 对叔丁基过氧化物（TBHP）诱导的氧化应激和损伤的影响。结果表明，BK 显著抑制 TBHP 诱导的 NPC 凋亡并恢复线粒体功能。进一步的分析表明，这种保护作用是通过 BK 受体 2（B2R）及其下游 PI3K/AKT 途径介导的。此外，还开发并验证了 BK/PLGA 缓释微球在大鼠模型中的疗效，突出了它们在 IVDD 治疗中的潜在疗效。总之，本研究揭示了 KKS 在 IVDD 发病机制中的关键作用，并表明靶向 B2R 是一种有前途的治疗策略，可延缓 IVDD 进展并促进椎间盘再生。
