Effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats

Abstract

Objective To evaluate the effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury (ALI) induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats. Methods Forty-five SPF healthy male Sprague-Dawley rats, weighing 200-220 g, were divided into 3 groups (n=15 each) using a random number table method: sham operation group (Sham group), ALI group and dexmedetomidine group (Dex group). A rat model of ALI was established by blunt chest trauma and hemorrhagic shock-resuscitation.Dexmedetomidine 5 μg·kg-1·h-1 was infused into the femoral vein after blunt chest trauma in Dex group.Blood samples were collected from the femoral artery at 6 h after blunt chest trauma for measurement of arterial oxygen partial pressure and concentrations of pro-inflammatory cytokines interleukin-1beta (IL-1β) and IL-18 in serum (by enzyme-linked immunosorbent assay). The oxygenation index was calculated.The rats were sacrificed and lungs were removed for examination of the pathological changes which were scored and for determination of the expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing CARD (ASC) in lung tissues (by Western blot) and activities of lactic dehydrogenase (LDH) and myeloperoxidase (MPO) in lung tissues (by colorimetry). Results Compared with Sham group, PaO2 and oxygenation index were significantly decreased, the expression of NLRP3, caspase-1 and ASC was up-regulated, the activities of LDH and MPO were increased, and the concentrations of IL-1β and IL-18 in serum were increased in ALI group (P<0.05). Compared with ALI group, PaO2 and oxygenation index were significantly decreased, the expression of NLRP3, caspase-1 and ASC was down-regulated, the activities of LDH and MPO were decreased, and the concentrations of IL-1β and IL-18 in serum were decreased in ALI group (P<0.05). Conclusion Dexmedetomidine can alleviate blunt chest trauma and hemorrhagic shock-resuscitation induced ALI in rats, and the mechanism is related to inhibition of NLRP3 inflammasome activation and reduction of inflammatory response. Key words: Dexmedetomidine; Acute lung injury; NLR family, pyrin domain-containing 3 protein