Background Acute lung injury (ALI) is a life-threatening respiratory disease with a high mortality rate, and there is a lack of effective targeted interventions.
Objective To explore the therapeutic effect of baricitinib on lipopolysaccharide (LPS) -induced acute lung injury in mice.
Methods A total of 36 male C57BL/6J mice aged 8 weeks were randomly divided into the control group (n=12), ALI group (n=12), and treatment group (ALI + baricitinib, n=12). The treatment group was given baricitinib 30 mg/kg intragastric administration once; one hour later, ALI group and treatment group were given a single tracheal infusion of LPS (10 mg/kg, dissolved in 50uL normal saline) to establish a mouse model of acute lung injury, while the control group was given tracheal infusion of equal dose of normal saline. After 24 h of endotracheal infusion of lipopolysaccharide or normal saline, the lung tissue and bronchoalveolar lavage fluid (BALF) were collected. The lung tissue injury was observed by hematoxylin-eosin (HE) staining. Vital capacity (VC), inspiratory capacity (IC), chord compliance (Cchord), and dyanamic compliance (Cdyn) were detected. The wet-dry mass(W/D) ratio of lung tissue was recorded. The total protein level in BALF was detected by the BCA protein quantitative method, and the total number of cells and neutrophils in BALF were analyzed. The levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in BALF were analyzed by ELISA. RT-qPCR was used to detect the transcription levels of IL-6, IL-1β and TNF-α in mouse lung tissue.
Results Compared with the control group, the lung tissue of the ALI group showed obvious lung injury, the lung function indexes decreased significantly (P < 0.001), while the lung tissue W/D was significantly increased (P < 0.001), and the protein concentration, cell number, and inflammatory factor levels in BALF were also significantly increased (P < 0.01). The expression level of inflammatory factors in lung tissue was significantly increased (P < 0.01). Compared with ALI group, the lung tissue injury of mice in the treatment group was significantly improved, the lung function index of Cdyn was increased (P < 0.05), the lung tissue W/D was decreased (P < 0.001), the protein concentration, cell number and inflammatory factors in BALF were decreased (P < 0.01). The expression level of inflammatory factors in lung tissue was decreased (P < 0.01).
Conclusion Baritinib pretreatment can alleviate acute lung injury induced by lipopolysaccharide to some extent.
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