期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 123, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2023.110789
关键词
TXNIP/Nrf2/NLRP3 axis; Verapamil; Intervertebral disc degeneration; Pyroptosis; ROS
This study validated the overexpression of TXNIP in intervertebral disc degeneration (IVDD) and investigated the therapeutic effects and mechanisms of action of verapamil. Verapamil mitigated oxidative stress and inflammasome activation in IVDD, protecting cells from pyroptosis, apoptosis, and extracellular matrix degradation. The Nrf2/TXNIP/NLRP3 axis played a major role in verapamil-mediated protection. In vivo, verapamil delayed the development of IVDD in a puncture-induced rat model. Overall, verapamil shows potential therapeutic effects in treating IVDD.
Low back pain is usually caused by intervertebral disc degeneration (IVDD), during which the involvement of oxidation system imbalance and inflammasome activation cannot be neglected. In this study, we aimed to validate the expression level of TXNIP in IVDD and investigate the function and potential mechanism of action of verapamil. TXNIP is upregulated in the degenerate nucleus pulposus in both humans and rats, as well as in tertbutyl hydroperoxide (TBHP)-stimulated nucleus pulposus cells. Administration of verapamil, a classic clinical drug, mitigated the TBHP-induced overproduction of reactive oxygen species and activation of the NLRP3 inflammasome, thus protecting cells from pyroptosis, apoptosis, and extracellular matrix degradation. The Nrf2/ TXNIP/NLRP3 axis plays a major role in verapamail-mediated protection. In vivo, a puncture-induced IVDD rat model was constructed, and we found that verapamil delayed the development of IVDD at both the imaging and histological levels. In summary, our results indicate the potential therapeutic effects and mechanisms of action of verapamil in the treatment of IVDD.
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