Effect of dexmedetomidine on acute lung injury induced by "double hit" in rats

Abstract

Objective To evaluate the effect of dexmedetomidine on acute lung injury (ALI) induced by double hit in rats. Methods Forty SPF male Sprague-Dawley rats, aged 8 weeks, weighing 215-225 g, were divided into 4 groups(n=10 each) using a random number table method: sham operation group (Sham group), double hit -induced ALI group (ALI group), double hit -induced ALI plus dexmedetomidine group (ALI+ Dex group) and double hit -induced ALI plus dexmedetomidine plus yohimbine group (ALI+ Dex+ Y group). ALI was induced by blunt chest trauma and hemorrhagic shock-resuscitation in pentobarbital sodium-anesthetized rats in ALI, ALI+ Dex and ALI+ Dex+ Y groups.In group ALI+ Dex, dexmedetomidine was intravenously infused for 10 min in a loading dose of 1 μg·kg-1·h-1 starting from the time point immediately after blunt chest trauma, followed by continuous infusion of 5 μg·kg-1·h-1 until the end of operation.Yohimbine 0.1 mg/kg was injected after giving the loading dose of dexmedetomidine and at 3 h after blunt chest trauma in ALI+ Dex+ Y group.Rats were sacrificed at 6 h after successful establishment of the model, blood samples were obtained for determination of concentrations of TNF-α and IL-6 in serum (by enzyme-linked immunosorbent assay), and lung tissues were obtained for determination of wet/dry weight (W/D) ratio, expression of Fas, FasL and caspase-3 in lung tissues (by SABC assay), cell apoptosis (by TUNEL), content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and for examination of the pathological changes which were scored.The apoptosis index (AI) was calculated. Results Compared with Sham group, the lung injury score, AI, levels of Fas, FasL, caspase-3 and MDA, and concentrations of TNF-α and IL-6 in serum were significantly increased, and the SOD activity in lung tissues was decreased in ALI group (P<0.05). Compared with ALI group, the lung injury score, AI, levels of Fas, FasL, caspase-3 and MDA, and concentrations of TNF-α and IL-6 in serum were significantly decreased, and the SOD activity in lung tissues was increased in ALI+ Dex and ALI+ Dex+ Y groups (P<0.05). Compared with group ALI+ Dex, the lung injury score, AI, levels of Fas, FasL, caspase-3 and MDA, and concentrations of TNF-α and IL-6 in serum were significantly increased, and the SOD activity in lung tissues was decreased in group ALI+ Dex+ Y (P<0.05). Conclusion Dexmedetomidine reduces ALI induced by double hit in rats, and the mechanism may be partially related to activating alpha-2 adrenergic receptor and inhibiting inflammatory responses, lipid peroxidation and cell apoptosis. Key words: Dexmedetomidine; Thoracic injury; Shock, hemorrhagic; Acute lung injury