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Limb ischemia\/reperfusion (I\/R) injury is a clinical syndrome associated with severe damages to skeletal muscles and other fatal outcomes. Oxidative stress and inflammatory response play vital roles in the development of limb I\/R injury. Existing evidence further indicates that Dl-3-n-butylphthalide (NBP) has anti-inflammatory and antioxidative properties. However, whether NBP can protect skeletal muscles from limb I\/R injury and the mechanism in mediating the action of NBP treatment still remain to be investigated, which are the focuses of the current study. Methods. The model of limb I\/R injury was established and H&amp;E staining was adopted to assess the pathological changes in skeletal muscles following limb I\/R injury. Additionally, the W\/D ratio of muscle tissue was also measured. ELISA and biochemical tests were carried out to measure the levels of inflammatory cytokines and oxidative stress in mouse models of limb I\/R injury. Moreover, the levels of the HMGB1\/TLR4\/NF-\u03baB pathway-related proteins were also determined using immunohistochemistry and immunoblotting. Results. It was established that NBP treatment alleviated I\/R-induced pathological changes in muscular tissue of mice, accompanied by lower W\/D ratio of skeletal muscular tissue. Meanwhile, the limb I\/R-induced inflammation and oxidative stress in skeletal muscles of mice were also inhibited by NBP. Mechanistic study indicated that the alleviatory effect of NBP was ascribed to inactivation of the HMGB1\/TLR4\/NF-\u03baB pathway. Conclusions. Our findings highlighted the potential of NBP as a novel strategy for limb I\/R-driven muscle tissue damages by suppressing inflammatory response and oxidative stress via the HMGB1\/TLR4\/NF-\u03baB pathway.<\/jats:p>","DOI":"10.1155\/2022\/5556067","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T23:50:14Z","timestamp":1664236214000},"page":"1-8","source":"Crossref","is-referenced-by-count":7,"title":["Dl-3-n-Butylphthalide (NBP) Mitigates Muscular Injury Induced by Limb Ischemia\/Reperfusion in Mice through the HMGB1\/TLR4\/NF-\u03baB Pathway"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3101-9260","authenticated-orcid":true,"given":"Huanhuan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-2114","authenticated-orcid":true,"given":"Jueqiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Laboratory of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3472-8801","authenticated-orcid":true,"given":"Wei","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0318-0559","authenticated-orcid":true,"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-4133","authenticated-orcid":true,"given":"Kui","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-4349","authenticated-orcid":true,"given":"Long","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3108-6401","authenticated-orcid":true,"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-3490","authenticated-orcid":true,"given":"Jinwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8570-7109","authenticated-orcid":true,"given":"Yanrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-9383","authenticated-orcid":true,"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020417"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13633"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-016-1258-x"},{"issue":"3","key":"4","first-page":"1139","article-title":"Lipoxin A4 pretreatment mitigates skeletal muscle ischemia-reperfusion injury in rats","volume":"9","author":"H. 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