Effect of ambroxol on p38 mitogen-activated protein kinase pathway in mice with sepsis-induced lung injury

Abstract

Objective To evaluate the effect of ambroxol on p38 mitogen-activated protein kinase pathway in mice with sepsis-induced lung injury. Methods Sixty male C57BL/6 mice were equally and randomly divided into 3 groups (n=20 each) using a random number table: sham operation group (group S), sepsis-induced lung injury group (group CLP), and sepsis-induced lung injury + ambroxol group (group AMB). Sespsis was produced by cecal ligation and puncture(CLP). Ambroxol 50 mg/kg preconditioning was injected intraperitoneally for 3 days in group AMB, while the equal volume of normal saline instead was given in S and VILI groups. The arterial blood gas was detected 24 h after CLP. Then the mice were sacrificed and broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of total protein, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and intercellular adhesion molecule-1 (ICAM-1). The lung tissues were taken for determination of wet to dry lung weight ratio (W/D ratio), expression of p-p38 MAPK, IL-1β mRNA, TNF-α mRNA, IL-6 mRNA and ICAM-1 mRNA, and for examination of the pathological changes which were scored. Results Compared with group S, partial pressure of oxygen in arterial blood(PaO2) was decreased (P<0.05), and W/D ratio, lung injury score, concentrations of total protein, IL-1β, TNF-α, IL-6 and ICAM-1 in BALF, and expression of p-p38 MAPK, IL-1β, TNF-α, IL-6 and ICAM-1 mRNA were significantly increased in CLP group (P<0.05). Compared with group CLP, PaO2 was increased (P<0.05), W/D ratio, lung injury score, concentrations of total protein, IL-1β, TNF-α, IL-6 and ICAM-1 in BALF, and expression of p-p38 MAPK, IL-1β, TNF-α, IL-6 and ICAM-1 mRNA were decreased in group AMB (P<0.05). Conclusion Ambroxol can attenuate sepsis-induced lung injury probably through inhibiting p38 mitogen-activated protein kinase pathway in mice. Key words: Ambroxol; Preconditioning; Sepsis-induced lung injury; p38 mitogen-activated protein kinase pathway