Abstract: Objective To investigate the protective effect of necrostatin-1 on ventilator - induced lung injury in rats. Methods Forty SD rats were randomly divided into four groups (n=10 for each group), spontaneous respiration group (group C), normal tidal volume (VT) group (group N), high VT group (group H) and necrostatin-1 group (group Nec-1). All rats were intubated after tracheotomy. Group C maintained spontaneous breathing, group N, group H and group Nec-1 were given mechanical ventilation with respective tidal volume (8 mL/kg, 40 mL/kg and 40 mL/kg). The group Nec-1 was injected Nec- 1 intravenously (1 mg/kg) before mechanical ventilation. After 4 hours of ventilation, samples of bronchoalveolar lavage fluid (BALF) and lung tissues were harvested. The infiltrated total cells, the total protein, the amount of interleukin (IL-6, IL-1β) and tumor necrosis factor - α (TNF-α) in alveolar lavage fluid were measured. The wet/dry weight ratio (W/D) of lung tissues was calculated. The histopathological changes of lung tissues were observed. The mRNA and protein expressions of receptor interacting protein 1 (RIPK1), RIPK3 and nuclear transcription factor -κB p65 (NF-κB p65) in lung tissues were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot assay respectively. Results There were no significant differences in related indexes in alveolar lavage fluid and lung tissue between group C and group N. Compared with those in group C and group N, values were increased in group H including the infiltrated total cells, the total protein and the amount of IL-6, IL-1β and TNF-α in alveolar lavage fluid, the wet/dry weight ratio and the histopathological score of lung tissues, the mRNA and protein expression levels of RIPK1, RIPK3 and NF-κB p65 in lung tissues (P＜0.01). In group Nec-1 the related indexes in alveolar lavage fluid and lung tissue were significantly lower than those of group H (P＜0.01). Conclusion RIPK1/RIPK3/NF-κB signaling pathway is involved in rat ventilatorinduced lung injury, and Nec-1 plays a protective role in rat lungs of ventilator-induced lung injury.

Key words: mechanical ventilation, ventilator-induced lung injury, animal experimentation, necrostatin-1