Propofol Protects Rats and Human Alveolar Epithelial Cells Against Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting HMGB1 Expression
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.
KEY WORDSpropofol HMGB1 LPS NF-κB TLR4 acute lung injury
This work was supported by the National Natural Science Foundation of China (NSF 30872433).
Xiaoyan Wang: conception, design, analysis, and interpretation of data; writing the manuscript.
Gongming Wang: conception, design, analysis, and interpretation of data; writing the manuscript.
Chengxiao Liu: analysis and interpretation of data; writing the manuscript.
Compliance with Ethical Standards
All procedures were performed in accordance with the Declaration of Helsinki of the World Medical Association. The study was approved by the ethics committee of Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Conflicts of Interest
The authors report no proprietary or commercial interest in any product mentioned, or concept discussed, in this article.
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