Protective effects of butorphanol in oleic acid-endotoxin “two-hit” induced rat lung injury by suppression of inflammation and apoptosis

• Published in: Scientific reports Vol. 14; no. 1; pp. 14231 - 10
• Main Authors: Zheng, Yanlei, Hu, Ronghua, Hu, Jinrong, Feng, Lina, Li, Shi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 692/308; 692/4017; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Acute Lung Injury - prevention & control; Animals; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; Blood gas analysis; Butorphanol; Butorphanol - pharmacology; Caspase-3; Cytokines - metabolism; Disease Models, Animal; Endotoxins; Flow cytometry; Histopathology; Humanities and Social Sciences; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Lipopolysaccharides; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung Injury - chemically induced; Lung Injury - drug therapy; Lung Injury - metabolism; Lung Injury - pathology; Lung Injury - prevention & control; Lungs; Male; multidisciplinary; NF-κB protein; Oleic acid; Rats; Rats, Sprague-Dawley; Science; Science (multidisciplinary); Transcription Factor RelA - metabolism; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-53483-5

Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a “two-hit” rat model and “two-hit” cell model to prove our hypothesis. Rats were divided into four groups [control, “two-hit” (OA + LPS), “two-hit” + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, “two-hit” (OA + LPS), “two-hit” + butorphanol (4 μM and 8 μM) (OA + LPS + 4 μM and OA + LPS + 8 μM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the “two-hit” induced lung injury, the expression of TNF, IL-1β, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the “two-hit” cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate “two-hit”-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.