Role of autophagy in ischemia postconditioning-induced attenuation of intestinal ischemia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of autophagy in ischemia postconditioning (IPO)-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 9-12 weeks, weighing 25-29 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (group S), intestinal I/R group (group IIR), group IPO and IPO plus 3-methyladenine (3-MA) group (group IPO+ 3-MA). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.The mice underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia before restoration of reperfusion in group IPO.Blood samples from the femoral artery were collected at 2 h of reperfusion for determination of concentrations of serum diamine oxidase (DAO), D-lactate (D-LA) and intestinal fatty acid binding protein (I-FABP). The animals were then sacrificed and intestinal tissues were removed for microscopic examination of the pathologic changes which were scored according to Chiu and for determination of the expression of autophagy-related proteins Beclin-1 and p62 (by Western blot). The water content of intestinal tissues was calculated. Results:Compared with group S, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly increased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in IIR, IPO and IPO+ 3-MA groups ( P<0.05). Compared with group IIR, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly decreased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in group IPO ( P<0.05). Compared with group IPO, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, and water content of intestinal tissues were significantly increased, LC3Ⅱ/LC3Ⅰratio was decreased, Beclin-1 expression was down-regulated, and p62 expression was up-regulated in group IPO+ 3-MA ( P<0.05). Conclusion:Autophagy is involved in ischemia postconditioning-induced attenuation of intestinal I/R injury in mice.