{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T11:11:38Z","timestamp":1760353898511,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Neurogenic intermittent claudication (NIC) pathogenesis associated with lumbar spinal stenosis (LSS) remains unclear. However, pyroptosis has been implicated in the pathogenesis of various central nervous system disorders. Therefore, the present study aimed to explore the potential role of pyroptosis in NIC progression. Additionally, the present study investigated the possible involvement of Sirtuin 1 (Sirt1), a protein recognized for its neuroprotective properties, in mitigating the progression of NIC by alleviating pyroptosis. In the current study, a rat model of NIC associated with LSS was successfully constructed by inserting a silicone strip into the vertebral plates. The Basso Beattie Bresnahan score was employed to assess the motor function of rats. Western blot analysis was performed to measure the levels of pyroptosis\u2010related proteins in rat spinal cord tissue. Meanwhile, PC\u201012 cells were cultured with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> to establish an in vitro model of oxidative stress, allowing to investigate the effects of Sirt1 on cell pyroptosis and oxidative stress in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated cells. The current results showed that rats with NIC developed both motor and sensory dysfunction. Additionally, NIC surgery notably elevated NOD\u2010, LRR\u2010, and pyrin domain\u2010containing protein 3 (NLRP3), apoptosis\u2010associated speck\u2010like protein containing a CARD (ASC), gasdermin D N\u2010terminal (GSDMD\u2010N), and IL\u20101\u03b2 levels in the spinal cord tissues of rats, suggesting that pyroptosis is activated in the context of NIC. Significantly, downregulation of Sirt1 exacerbated malondialdehyde and reactive oxygen species levels, and simultaneously reduced GSH levels in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010stimulated PC\u201012 cells, suggesting that Sirt1 deficiency can aggravate oxidative stress. Meanwhile, downregulation of Sirt1 also led to increased levels of NLRP3, ASC, GSDMD\u2010N, and cleaved caspase 1 in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010stimulated PC\u201012 cells, suggesting that Sirt1 deficiency can further enhance the pyroptosis in these cells. Targeting pyroptosis signaling may yield new insights into the treatment of NIC. The mechanisms mediated by pyroptosis could offer valuable perspectives on the pathogenesis and management of this condition.<\/jats:p>","DOI":"10.1002\/ddr.70083","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T14:19:42Z","timestamp":1744121982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sirtuin 1 Is a Potential Target for the Treatment of Neurogenic Intermittent Claudication by Modulating Pyroptosis"],"prefix":"10.1002","volume":"86","author":[{"given":"Xuejian","family":"Dan","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Tongji University School of Medicine, Divison of Spine Tongji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Jiaotong University School of Medicine (Punan Hospital in Pudong New District) Punan Branch of Renji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Tongji University School of Medicine, Divison of Spine Tongji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Tongji University School of Medicine, Divison of Spine Tongji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Tongji University School of Medicine, Divison of Spine Tongji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Tongji University School of Medicine, Divison of Spine Tongji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5966-0271","authenticated-orcid":false,"given":"Bin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Tongji University School of Medicine, Divison of Spine Tongji Hospital Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133153"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-057724"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1995.12.1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.04.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2023.2285707"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0106-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2012\/15\/451"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201302451"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-023-01790-4"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3791\/65456"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-024-09568-5"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.026"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06221-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.13.9.27"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000016662"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2024.130564"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109026"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.274349"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29071415"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108671"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-011-1873-8"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b17-00856"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8111354"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58030384"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061101"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101781"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-024-01043-4"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1515\/tnsci-2022-0326"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1283"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/wjps-2023-000602"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9443"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.040"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2102072"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2024.114061"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110180"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00729-9"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-022-00594-4"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T10:45:05Z","timestamp":1760352305000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/ddr.70083"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70083","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"type":"print","value":"0272-4391"},{"type":"electronic","value":"1098-2299"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2025-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70083"}}