Effects Of SLC7A11 In Dexmedetomidine Pretreatment To Attenuate Ferroptosis Caused By Intestinal Ischemia-reperfusion Injury

Objective:To evaluate the effects of SLC7A11 in dexmedetomidine pretreatment to attenuate ferroptosis caused by intestinal ischemia-reperfusion injury in mice.Methods:Twenty-four healthy meal SPF C57BL/6J mice,aged 8 weeks,weighing 22～25g,were randomly divided into Sham operation group（S group）,intestinal I/R group（II/R group）,dexmedetomidine group（DEX group）and dexmedetomidine plus SLC7A11 inhibitior group（DIKE group）,with 6 mice in each group.Intestinal ischemia was induced by occluding the superior mesenteric artery for45 min followed by 30 min of reperfusion to establish the model of II/R injury.In DEX and DIKE groups,Dexmedetomidine 25μg/kg was intraperitoneally injected at30 min before clamping the superior mesenteric artery.The same amount of normal saline was injected in the S group and the II/R group.In DIKE group,SLC7A11inhibitior Imidazole ketone erastin 50mg/kg was intraperitoneally injected at 90 min before ischemia.Mice were sacrificed 30min after reperfusion,and small intestinal tissues in length 5 cm away from the ileocecal valvum were obtained for microscopic examination of pathological changes of intestinal mucosa and for determination of contents of Fe²⁺and malondialdehyde（MDA）and superoxide dismutase（SOD）activity（by colometry）,reduced glutathione（GSH）content（by Microplate method）,and expression of SLC7A11,glutathione peroxidase 4（by Western blot）.Intestinal damage was assessed and scored according to Chiu.Results:Compared with group S,the Chiu’s score,Fe²⁺and MDA contents were significantly increased,the SOD activity and GSH content were decreased,and the expression of SLC7A11 and GPX4 was down-regulated in the other 3 groups（P<0.05）.Compared with group II/R,the Chiu’s score,Fe²⁺and MDA contents were significantly decreased,the SOD activity and GSH content were increased,and the expression of SLC7A11 and GPX4 was up-regulated in group DEX（P<0.05）.Compared with group DEX,Chiu’s score,Fe²⁺and MDA content were significantly increased,the SOD activity and GSH content were decreased,and the expression of SLC7A11 and GPX4 was down-regulated in group DIKE（P<0.05）.Conclusion:1.Ferroptosis occurs in intestinal ischemia-reperfusion injury;2.Dexmedetomidine pretreatment attenuates intestinal ischemia-reperfusion injury in mice through inhibition of ferroptosis;3.Activation of SLC7A11 plays a protective role in the reduction of ferroptosis caused by intestinal ischemia-reperfusion injury in mice with dexmedetomidine.