Protective effect of Ghrelin on ventilator induced lung injury through vagus nerve in rats

Objective To investigate whether Ghrelin protects against ventilator induced lung injury through vagus nerve in rats. Methods 48 healthy male SD rats were randomly divided into six groups (eight in each group): conventional mechanical ventilation group (LV group, tidal volume=8 ml/kg), high tidal volume ventilation group (VILI group, tidal volume=30 ml/kg), Ghrelin+ high tidal volume ventilation group (GH+ VILI group), vagotomy+ high tidal volume ventilation group (Vag+ VILI group), sham vagotomy+ high tidal volume ventilation group (Sham+ VILI group), Ghrelin+ vagotomy+ high tidal volume ventilation group (GH+ Vag+ VILI group). Right vagotomy was performed at 1 h before ventilation in each vagotomy group.Ghrelin (10 nmol) was injected intraperitoneally at 30 min before mechanical ventilation in each Ghrelin group, and VILI group was injected with normal volume saline.Each group took mechanical ventilation for four hours and heart rate, mean arterial pressure, oxygenation index, lung elastic resistance were examined hourly.At the end of the experiment, the rats were executed to take lung tissue, lung wet/dry weight ratio (W/D) and myeloperoxidase (MPO) activity were examined, the levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay. Results During the mechanical ventilation, the mean arterial pressure in each group was stable and there was no statistical difference.Compared with the LV group, the oxygenation indexe in VILI group was decreased obviously and lung elastic resistance was significantly increased at each time point (all P<0.05), lung W/D ratio, MPO level, the levels of inflammatory factors TNF-α and IL-8 in BALF were increased significantly (all P<0.05). Compared with the VILI group, the oxygenation index in GH+ VILI group was significantly higher and lung elastic resistance was significantly decreased at each time point (all P<0.05), lung W/D ratio, MPO level, the levels of inflammatory factors TNF-α and IL-8 in BALF were decreased significantly (all P<0.05). There was no statistical difference in the oxygenation index, lung elastic resistance, lung W/D ratio, MPO level and the levels of inflammatory factors TNF-α and IL-8 in BALF between VILI group and GH+ Vag+ VILI group. Conclusions Ghrelin palys protective roles in ventilator induced lung injury by activating the vagus nerve. Key words: Ghrelin; Ventilator induced lung injury; Cholinergic anti-inflammatory pathway; Cytokines