Effect of remifentanil on MAPK signaling pathway during intestinal epithelial cell apoptosis induced by intestinal ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of remifentanil on mitogen-activated protein kinase (MAPK) signaling pathway during intestinal epithelial cell apoptosis induced by intestinal ischemia-reperfusion (I/R) in rats.Methods:Thirty-six clean grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, aged 2 months, were divided into 3 groups ( n=12 each) by a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group) and remifentanil group (R group). Intestinal I/R was produced by occlusion of superior mesenteric artery for 1 h followed by reperfusion in anesthetized rats.At 30 min before ischemia, 0.2 μg·kg -1·min -1 of remifentanil was infused intravenously for 5 min , followed by infusion of normal saline for 5 min, repeating for 3 cycles in group R. At 2 h of reperfusion, blood samples were collected from right ventricle to measure the concentration of diamine oxidase (DAO). The animals were then sacrificed and the intestinal tissues were obtained for examination of pathological changes and scored according to Chiu, for calculation of intestinal epithelial cell apoptosis rate (by TUNEL), for determination of the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated p38 MAPK (p-p38 MAPK), cleaved caspase-3 and nuclear factor kappa B p65 (NF-κB p65) in nucleoprotein and for calculation of p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio in the intestinal tissues. Results:Compared with group Sham, Chiu′s scores, serum DAO concentration, apoptosis rate, p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio and the expression of cleaved caspase-3 and NF-κB p65 in the intestinal tissues were significantly increased in group I/R, and Chiu′s scores was increased ( P<0.05), and no significant change was found in serum DAO concentration, apoptosis rate, p-ERK/ERK ratio, p-JNK/JNK ratio, p-p38 MAPK/p38 MAPK ratio and the expression of cleaved caspase-3 and NF-κB p65 in the intestinal tissues in group R ( P>0.05). Compared with group I/R, Chiu′s scores, apoptosis rate, serum DAO concentration, p-ERK/ERK ratio and expression of cleaved caspase-3 and NF-κB p65 were significantly decreased in group R ( P<0.05). Conclusion:The mechanism by which remifentanil inhibits intestinal epithelial cell apoptosis induced by intestinal I/R is related to promoting activation of ERK in rats.