Role of cholinergic anti-inflammatory pathway in dexmedetomidine pretreatment-induced reduction of acute lung injury in a rat model of intestinal ischemia-reperfusion

Abstract

Objective To evaluate the role of cholinergic anti-inflammatory pathway in dexmedetomidine pretreatment-induced reduction of acute lung injury in a rat model of intestinal ischemia-reperfusion (I/R). Methods Twenty-four healthy male Sprague-Dawley rats, aged 2-3 months, weighing 200-250 g, were divided into 4 groups (n=6) using a random number table method: sham operation group (S group), intestinal I/R group (II/R group ), dexmetomidine group (DEX group) and α7 nicotinic acetylcholine receptor antagonist α-bungarotoxin (α-BGT) group (α-BGT group). Intestinal I/R was produced by occlusion of the superior mesenteric artery (SMA) for 60 min followed by 120 min of reperfusion in anesthetized rats.Dexmetomidine 5 μg·kg-1·h-1 was injected via the tail vein at 1 h before operation in DEX group and α-BGT group.α-BGT 1 μg/kg was intraperitoneally injected at 15 min before dexmetomidine injection in α-BGT group.Rats were sacrificed at 120 min of reperfusion, and lung tissues were obtained for microscopic examination of pathological changes (with a light microscope) and for determination of wet/dry weight ratio (W/D ratio), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents (using enzyme-linked immunosorbent assay), malondialdehyde (MDA) content (using thiobarbital acid method) and superoxide dismutase (SOD) activity (by xanthine oxidase method). Results Compared with group S, the W/D ratio and contents of MDA, TNF-α and IL-6 were significantly increased, and the SOD activity was decreased in II/R and α-BGT groups, and TNF-α and IL-6 contents were significantly increased in group DEX (P<0.05). Compared with group II/R, the W/D ratio and contents of MDA, TNF-α and IL-6 were significantly decreased, SOD activity was increased (P<0.05), and the pathological changes were significantly attenuated in group DEX.Compared with group DEX, the W/D ratio and contents of MDA, TNF-α and IL-6 were significantly increased, SOD activity was decreased (P<0.05), and the pathological changes were accentuated in group α-BGT. Conclusion Activation of cholinergic anti-inflammatory pathway is involved in the mechanism by which dexmedetomidine pretreatment reduces acute lung injury in a rat model of intestinal I/R. Key words: Acetylcholine; Dexmetomidine; Reperfusion injury; Intestines; Hespiratory distress syndrome, adult