Changes in expression of caspase recruitment domain protein 3 during ventilator-induced lung injury in rats

Abstract

Objective To evaluate the changes in the expression of caspase recruitment domain protein 3 (NLRC3) during ventilator-induced lung injury (VILI) in rats. Methods Twenty-four clean-grade healthy adult male Sprague-Dawley rats, aged 8 weeks, weighing 180-220 g, were divided into 2 groups (n=12 each) according to the random number table method: control group (group C) and group VILI.Both groups underwent tracheotomy and intubation, group C kept spontaneous breathing, and the animals were mechanically ventilated, with tidal volume 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, fraction of inspired oxygen 21%, and positive end-expiratory pressure 0 in group VILI.The rats were sacrificed 4 h later, bronchoalveolar lavage fluid (BALF) was collected for determination of concentrations of interleukin-1beta (IL-1β)and IL-18 in BALF (by enzyme-linked immunosorbent assay), and lung tissues were obtained for examination of the pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio) and expression of nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3 (NLRC3), NOD-like receptor pyrin domain containing 3 (NLRP3), ASC and caspase-1 protein and mRNA (by Western blot and real-time polymerase chain reaction). Results Compared with group C, the score of pathological damage to lung tissues, W/D ratio, and concentrations of IL-1β and IL-18 in BALF were significantly increased, the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was up-regulated, and the expression of NLRC3 protein and mRNA in lung tissues was down-regulated in group VILI (P<0.05). Conclusion The mechanism of VILI may be related to down-regulating NLRC3 expression and activating NLRP3 inflammasomes in rats. Key words: Ventilator-induced lung injury; NLR family, pyrin domain-containing 3 protein