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褪黑素通过诱导自噬和抑制细胞凋亡的潜在机制来改善椎间盘退变。

Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition.

机构信息

Department of Orthopaedic Surgery, The Second Afliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, China.

出版信息

J Cell Mol Med. 2019 Mar;23(3):2136-2148. doi: 10.1111/jcmm.14125. Epub 2019 Jan 4.

DOI:10.1111/jcmm.14125
PMID:30609271
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6378230/
Abstract

Intervertebral disc degeneration (IDD) is a complicated disease in patients. The pathogenesis of IDD encompasses cellular oxidative stress, mitochondrion dysfunction and apoptosis. Melatonin eliminates oxygen free radicals, regulates mitochondrial homoeostasis and function, stimulates mitophagy and protects against cellular apoptosis. Therefore, we hypothesize that melatonin has beneficial effect on IDD by mitophagy stimulation and inhibition of apoptosis. The effects of melatonin on IDD were investigated in vitro and in vivo. For the former, melatonin diminished cellular apoptosis caused by tert-butyl hydroperoxide in nucleus pulposus (NP) cells. Mitophagy, as well as its upstream regulator Parkin, was activated by melatonin in both a dose and time-dependent manner. Mitophagy inhibition by cyclosporine A (CsA) partially eliminated the protective effects of melatonin against NP cell apoptosis, suggesting that mitophagy is involved in the protective effect of melatonin on IDD. In addition, melatonin was demonstrated to preserve the extracellular matrix (ECM) content of Collagen II, Aggrecan and Sox-9, while inhibiting the expression of matrix degeneration enzymes, including MMP-13 and ADAMTS-5. In vivo, our results demonstrated that melatonin treatment ameliorated IDD in a puncture-induced rat model. To conclude, our results suggested that melatonin protected NP cells against apoptosis via mitophagy induction and ameliorated disc degeneration, providing the potential therapy for IDD.

摘要

椎间盘退变（IDD）是一种复杂的疾病。IDD 的发病机制包括细胞氧化应激、线粒体功能障碍和细胞凋亡。褪黑素能消除氧自由基，调节线粒体的平衡和功能，刺激自噬，防止细胞凋亡。因此，我们假设褪黑素通过刺激自噬和抑制细胞凋亡对 IDD 有有益的作用。本文研究了褪黑素对体外和体内 IDD 的作用。体外实验中，褪黑素可减少核髓核细胞（NP）中叔丁基过氧化物引起的细胞凋亡。褪黑素以剂量和时间依赖的方式激活自噬及其上游调控因子 Parkin。自噬抑制剂环孢素 A（CsA）部分消除了褪黑素对 NP 细胞凋亡的保护作用，提示自噬参与了褪黑素对 IDD 的保护作用。此外，褪黑素还能保持细胞外基质（ECM）中 Collagen II、Aggrecan 和 Sox-9 的含量，同时抑制基质降解酶 MMP-13 和 ADAMTS-5 的表达。在体内，实验结果表明褪黑素治疗可改善穿刺诱导的大鼠模型中的 IDD。综上所述，褪黑素通过诱导自噬来保护 NP 细胞免于凋亡，改善椎间盘退变，为 IDD 提供了潜在的治疗方法。

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Oncotarget. 2017 Mar 28;8(13):20988-21000. doi: 10.18632/oncotarget.15470.
2
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3
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Front Pharmacol. 2025 Apr 1;16:1579507. doi: 10.3389/fphar.2025.1579507. eCollection 2025.
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