Verapamil attenuates intervertebral disc degeneration by suppressing ROS overproduction and pyroptosis via targeting the Nrf2/TXNIP/NLRP3 axis in four-week puncture-induced rat models both in vivo and in vitro

被引：7
|
作者：
Chen, Yan [1 ,2 ]
Cao, Xiankun [1 ,2 ]
Pan, Bin [1 ,2 ]
Du, Han [1 ,2 ]
Li, Baixing [1 ,2 ]
Yang, Xiao [1 ,2 ]
Chen, Xuzhuo [3 ,4 ]
Wang, Xin [1 ,2 ]
Zhou, Tangjun [1 ,2 ]
Qin, An [1 ,2 ,5 ]
Zhao, Changqing [1 ,2 ,5 ]
Zhao, Jie [1 ,2 ]
机构：
[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Sch Med, Shanghai 200011, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Shanghai Key Lab Orthopaed Implants, Shanghai 200011, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Coll Stomatol, Natl Clin Res Ctr Oral Dis,Sch Med,Dept Oral Surg,, Shanghai 200011, Peoples R China
[4] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Shanghai Res Inst Stomatol, Coll Stomatol,Sch Med,Natl Clin Res Ctr Oral Dis, Shanghai 200011, Peoples R China
[5] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed, Shanghai Key Lab Orthopaed Implants,Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2023年 / 123卷
关键词：
TXNIP/Nrf2/NLRP3; axis; Verapamil; Intervertebral disc degeneration; Pyroptosis; ROS; NF-KAPPA-B; OXIDATIVE STRESS; PHARMACOLOGICAL-PROPERTIES; NLRP3; INFLAMMASOME; APOPTOSIS; BLOCKERS;
D O I：
10.1016/j.intimp.2023.110789
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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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页数：13
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