Protective effect of neurotensins and its mechanism in LPS-induced acute lung injury

Abstract

Objective To investigate the protective effect of neurotensins on inflammatory responses in mice with LPS-induced acute lung injury. Methods 100 specific-pathogen free C57BL/6 mice (20-25 g, 6-8 weeks, 50 males and 50 females) were obtained from the Shanghai Laboratory Animal Center (SLAC) (Shanghai, China). All animals were randomly divided into five groups:① Normal control group: mice were treated with 60 μl PBS intratracheally;② LPS-induced acute lung injury group: mice were treated with 60 μg LPS intratracheally;③ 20 mg/kg neurotensins treated ALI group: mice were subjected to LPS-induced ALI and treated with 20 mg/kg Nts via tail vein injection 1 hour after LPS challenge;④ 40 mg/kg neurotensins treated ALI group: mice were subjected to LPS-induced ALI and treated with 40 mg/kg Nts via tail vein injection 1 hour after LPS challenge;⑤ 80 mg/kg neurotensins treated ALI group: mice were subjected to LPS-induced ALI and received 80 mg/kg Nts treatment via tail vein injection. The severity of lung injury, MPO acitvity, neutrophils infilatration, lung edema, and pro-inflammatory cytokines concentration in BALF were assessed 24 hours after ALI. Results Compared with the control group of mice, LPS induction significantly increased the severity of lung injury, including the lung edema, inflammatory cell infiltration, and the production of inflammatory cytokines in BALF (TNF-α, IL-6, IL-1β, and MCP-1). However, Neurotensins treatment obviously attenuated the lung injury caused by LPS induction, including the lung edema, the infiltration of inflammatory cells , and the secretion of inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1). Meanwhile, the protective effect is dosage dependent. Conclusion Neurotensins have a protective effect on LPS-induced acute lung injury in mice, and the protective mechanisms may be related to block the tachykinins mediated inflammatory pathways activation. Key words: Neurotensins; Tachykinins; Inflammatory response; Acute lung injury