Protective effects of ghrelin in ventilator-induced lung injury in rats

•Repeated mechanical stretching results in the release of inflammatory cytokines in the lung.•Cytokines induced inflammatory damage is the main pathogenesis of VILI.•Ghrelin can attenuate VILI via inhibit cytokines release through TLR4/NF-κB pathway.

Ghrelin has exhibited potent anti-inflammatory effects on various inflammatory diseases. The aim of this study was to investigate the potential effects of ghrelin on a model of ventilator-induced lung injury (VILI) established in rats. Male Sprague-Dawley rats were randomly divided into three groups: low volume ventilation (LV, Vt = 8 ml/kg) group, a VILI group (Vt = 30 ml/kg), and a VILI group pretreated with ghrelin (GH + VILI). For the LV group, for the VILI and GH + VILI groups, the same parameters were applied except the tidal volume was increased to 40 ml/kg. After 4 h of MV, blood gas, lung elastance, and levels of inflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and (MIP)-2 and total protein in bronchoalveolar lavage fluid (BALF) were analyzed. Myeloperoxidase (MPO), (TLR)-4, and NF-κB, were detected in lung tissues. Water content (wet-to-dry ratio) and lung morphology were also evaluated. The VILI group had a higher acute lung injury (ALI) score, wet weight to dry ratio, MPO activity, and concentrations of inflammatory mediators (TNF-α, IL-6, IL-1β, and MIP-2) in BALF, as well as higher levels of TLR4 and NF-κB expression than the LV group (P < 0.05). All histopathologic ALI, the inflammatory profile, and pulmonary dynamics have been improved by ghrelin pretreatment (P < 0.05). Ghrelin pretreatment also decreased TLR4 expression and NF-κB activity compared with the VILI group (P < 0.05). Ghrelin pretreatment attenuated VILI in rats by reducing MV-induced pulmonary inflammation and might represent a novel therapeutic candidate for protection against VILI.