title: Propofol Protects Rats and Human Alveolar Epithelial Cells Against Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting HMGB1 Expression.
abstract: High-mobility group box 1 (HMGB1) plays a key role in the development of acute lung injury (ALI). Propofol, a general anesthetic with anti-inflammatory properties, has been suggested to be able to modulate lipopolysaccharide (LPS)-induced ALI. In this study, we investigated the effects of propofol on the expression of HMGB1 in a rat model of LPS-induced ALI. Rats underwent intraperitoneal injection of LPS to mimic sepsis-induced ALI. Propofol bolus (1, 5, or 10 mg/kg) was infused continuously 30 min after LPS administration, followed by infusion at 5 mg/(kg · h) through the left femoral vein cannula. LPS increased wet to dry weight ratio and myeloperoxidase activity in lung tissues and caused the elevation of total protein and cells, neutrophils, macrophages, and neutrophils in bronchoalveolar lavage fluid (BALF). Moreover, HMGB1 and other cytokine levels were increased in BALF and lung tissues and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. Propofol inhibited all the above effects. It also inhibited LPS-induced toll-like receptor (TLR)2/4 protein upexpression and NF-κB activation in lung tissues and human alveolar epithelial cells. Propofol protects rats and human alveolar epithelial cells against HMGB1 expression in a rat model of LPS-induced ALI. These effects may partially result from reductions in TLR2/4 and NF-κB activation.
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong, China.
authors.forename: Chengxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong, China. gongmingwang666@outlook.com.
authors.forename: Gongming
authors.initials: G
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D056809:Alveolar Epithelial Cells / Q000187:drug effects*; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015742:Propofol
keywords: HMGB1; LPS; NF-κB; TLR4; acute lung injury; propofol