{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:32:00Z","timestamp":1751463120523},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,4,20]],"date-time":"2016-04-20T00:00:00Z","timestamp":1461110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Levobupivacaine (<jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content>), a kind of local anesthetic, possesses anti\u2010inflammatory properties. High\u2010mobility group box 1 (<jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>1), a nuclear <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding protein, plays a key role in the development of acute lung injury (<jats:styled-content style=\"fixed-case\">ALI<\/jats:styled-content>). The aim of this study was to investigate whether <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> attenuates <jats:styled-content style=\"fixed-case\">ALI<\/jats:styled-content> by the inhibition of <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>1 expression and to investigate the molecular mechanisms. <jats:styled-content style=\"fixed-case\">ALI<\/jats:styled-content> in male rats was induced by an intratracheal instillation of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (5 mg\/kg), and male rats received mini\u2010osmotic pumps containing <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> 30 min after <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure. A549 alveolar epithelial cells were incubated with <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> in the presence or absence of <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content>. An enzyme\u2010linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blotting was used to detect the changes in the expression of toll\u2010like receptor 2\/4 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2\/4) and the activation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB. The results showed that <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> significantly protected animals from <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">ALI<\/jats:styled-content> as evidenced by a decrease in the ratio of lung wet to dry weight, total cells, neutrophils, macrophages, and myeloperoxidase activity, associated with a reduced lung histological damage. We also found that <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> post\u2010treatment markedly inhibited the release of <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>1 and other pro\u2010inflammatory cytokines. Furthermore, <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> significantly inhibited <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2\/4 protein overexpression and <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation in the lung tissues and in <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010stimulated A549 alveolar epithelial cells in vitro. These data indicate that <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> attenuated <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">ALI<\/jats:styled-content> by the inhibition of <jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>1 expression in rats. These benefits were associated with the inhibition of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2\/4\u2010<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB pathway by <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/fcp.12197","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T07:23:50Z","timestamp":1458372230000},"page":"307-315","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Levobupivacaine attenuates lipopolysaccharide\u2010induced acute lung injury"],"prefix":"10.1111","volume":"30","author":[{"given":"Dan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital of Henan University of Science and Technology Luoyang Henan China 471000"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kehan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital of Henan University of Science and Technology Luoyang Henan China 471000"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muqiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital of Henan University of Science and Technology Luoyang Henan China 471000"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital of Henan University of Science and Technology Luoyang Henan China 471000"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafei","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology First Affiliated Hospital of Henan University of Science and Technology Luoyang Henan China 471000"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.5492\/wjccm.v1.i2.50"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2009.02255.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.10.009"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000000602"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12463"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.909730"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2014.00176"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.863876"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"e_1_2_7_11_1","first-page":"245","article-title":"High mobility group box 1 protein as a late\u2010acting mediator of acute lung inflammation","volume":"17","author":"Lutz W.","year":"2004","journal-title":"Int. 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