ABSTRACT
Objective To evaluate the role of cholinergic anti-inflammatory pathway in dexmedeto-midine 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 acetyl-choline receptor antagonistα-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 anesthe-tized rats. Dexmetomidine 5 μg·kg-1 ·h-1 was injected via the tail vein at 1 h before operation in DEX group andα-BGT group. α-BGT 1μg∕kg was intraperitoneally injected at 15 min before dexmetomidine in-jection 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-αand IL-6 were significantly increased, and the SOD activi-ty 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-αand 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 path-way is involved in the mechanism by which dexmedetomidine pretreatment reduces acute lung injury in a rat model of intestinal I∕R.
ABSTRACT
Objective To evaluate the effect of dexmedimidine on intestinal injury in rats with endotoxemia.Methods Twenty-four healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 200-250 g,were divided into 4 groups (n =6 each) using a random number table method:control group (group C),endotoxemia group (group E),dexmedimidine group (group D) and dexmedimidine plus α7 subunit-containing nicotinic acetylcholine receptor antagonist group (D +α-BGT group).The endotoxemia model was established by injecting lipopolysaccharide (LPS) 10 mg/kg via the femoral vein.Dexmedetomidine 40 μg/kg was injected and 15 min later LPS was intravenously injected in group D.Dexmedetomidine 40 μg/kg was intraperitoneally injected after intraperitoneal injection of α-bungarotoxin 1 μg/kg,and 15 min later LPS was intravenously injected in group D+o-BGT.Blood samples were collected from the abdominal aorta at 6 h after LPS injection for determination of the plasma interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay).Rats were sacrificed after blood sampling,and intestinal tissues were obtained for examination of the pathological changes and for determination of the myeloperoxidase (MPO) activity (by chemical colorimetry) and expression of NF-κB p65 in nucleoprotein (by Western blot).Results Compared with group C,the plasma IL-6 and TNF-o concentrations and MPO activity in intestinal tissues were significantly increased,and the expression of NF-κB p65 in nucleoprotein was up-regulated in the other 3 groups (P＜0.05).Compared with group E,the plasma IL-6 and TNF-α concentrations and MPO activity in intestinal tissues were significantly decreased,the expression of NF-κB p65 in nucleoprotein was down-regulated (p＜0.05),and the pathological changes of intestinal tissues were significantly attenuated in group D.Compared with group D,the plasma IL-6 and TNF-α concentrations and MPO activity in intestinal tissues were significantly increased,the expression of NF-κB p65 in nucleoprotein was up-regulated (P＜0.05),and the pathological changes of intestinal tissues were accentuated in group D+α-BGT.Conclusion Dexmedetomidine can reduce the intestinal injury in rats with endotoxemia,and the mechanism may be related to activating cholinergic anti-inflammatory pathway and further inhibiting inflammatory responses.