Effect of dexmedetomidine on endoplasmic reticulum stress during intestinal ischemia-reperfusion in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on endoplasmic reticulum stress during intestinal ischemia-reperfusion (I/R) in mice.Methods Thirty SPF healthy male C57BL/6 mice,aged 8 weeks,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (S group),intestinal I/R group (I/R group) and dexmedetomidine group (DEX group).The superior mesenteric artery was only isolated but not clamped in S group.The model of intestinal I/R injury was established by clamping superior mesenteric artery for 20 min followed by 24 h of reperfusion in I/R group and DEX group.Dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in DEX group,while the equal volume of normal saline was given instead of dexmedetomidine in S group and I/R group.Mice were sacrificed at 24 h of reperfusion,and small intestinal tissues was obtained for examination of the pathological changes and ultrastructure of intestinal epithelial cells and for determination of cell apoptosis,expression of CCAAT-enhancer binding protein homologous protein (CHOP),transcription factors (ATF4),and X-4 box binding protein 1 (XBP1) mRNA (by real-time polymerase chain reaction),and expression of CHOP,Bcl-2,Bax and caspase-3 in intestinal tissues (by Western bolt).The apoptosis index (AI) and ratio of Bcl-2 to Bax were calculated.Intestinal damage was assessed and scored according to Chiu.Results Compared with S group,Chiu's score and AI were significantly increased,the expression of CHOP,ATF4 and XBP-1 mRNA,CHOP,Bax and caspase-3 was up-regulated,and the expression of Bcl-2 was down-regulated,and Bcl-2/Bax ratio was decreased in I/R group and DEX group (P＜0.05).Compared with I/R group,Chiu's score and AI were significantly decreased,the expression of CHOP,ATF4 and XBP-1 mRNA,CHOP,Bax and caspase-3 was down-regulated,and the expression of Bcl-2 was up-regulated,and Bcl-2/Bax ratio was increased in DEX group (P＜0.05).Conclusion The mechanism by which dexmedetomidine reduces intestinal I/R injury may be related to regulating endoplasmic reticulum stress and inhibiting cell apoptosis in mice.