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Inhibition of pyroptosis may be a way to alleviate inflammation as well as tissue damage triggered after lipopolysaccharide (LPS) stimulation. The aim of the present study was to explore whether buformin (BF), a hypoglycemic agent, could alleviate sepsis-induced ALI by inhibiting pyroptosis.<\/jats:p>\n               <jats:p>Methods: Wildtype C57BL\/6 mice were randomly divided into control group, BF group, LPS group and LPS+BF group. BF group and LPS+BF group were pretreated with BF at a dose of 25 mg\/kg, and the changes were observed. In addition, BF was used to interfere with THP-1 cells. The therapeutic effect of BF has been verified by intraperitoneal injection of BF in vivo after LPS stimulation.<\/jats:p>\n               <jats:p>Results: Inflammation and injury was significantly reduced in BF pretreated mice, and the indexes related to pyroptosis were suppressed. The phosphorylation of AMP-activated protein kinase (AMPK) in lung tissues of mice in the BF and LPS+BF groups was significantly higher. In THP-1 cells, the AMPK inhibitor, Compound C was added to demonstrate that BF worked via AMPK to inhibit NLRP3 inflammasome. It was further demonstrated that BF up-regulated autophagy, which in turn promoted NLRP3 inflammasome degradation. On the other hand, BF decreased NLRP3 mRNA level by increasing nuclear factor-erythroid 2 related factor 2 (Nrf2). And BF showed a therapeutic effect after LPS challenge.<\/jats:p>\n               <jats:p>Conclusion: Our study confirmed that BF inhibited NLRP3-mediated pyroptosis in sepsis-induced ALI by up-regulating autophagy and Nrf2 protein level through an AMPK-dependent pathway. This provides a new strategy for clinical mitigation of sepsis-induced ALI.<\/jats:p>","DOI":"10.1042\/cs20211156","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T11:08:52Z","timestamp":1644318532000},"page":"273-289","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Buformin alleviates sepsis-induced acute lung injury via inhibiting NLRP3-mediated pyroptosis through an AMPK-dependent pathway"],"prefix":"10.1042","volume":"136","author":[{"given":"Bohao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guorui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinglv","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-5084","authenticated-orcid":false,"given":"Qing","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"2022022108541511400_B1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.5858\/arpa.2015-0519-RA","article-title":"Acute lung injury: a clinical and molecular review","volume":"140","author":"Butt","year":"2016","journal-title":"Arch. 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