关键词: SLC7A11, 铁死亡, 肠, 再灌注损伤, 右美托咪定

Abstract: AIM: To evaluate the effect of SLC7A11 in dexmedetomidine pretreatment induced reduction of ferroptosis caused by intestinal ischemia-reperfusion (II/R) injury in mice.  METHODS: Twenty-four healthy meal SPF C57BL/6J mice, aged 8 weeks, weighing 22-25 g, 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 for 45 min followed by 30 min of reperfusion to establish the model of II/R injury. In DEX and DIKE groups, Dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 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, SLC7A11 inhibitior Imidazole ketone erastin 50 mg/kg was intraperitoneally injected at 90 min before ischemia. Mice were sacrificed 30 min 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, 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). Intraperitoneal injection of dexmedetomidine significantly decreased Chiu's score, Fe2+ and MDA contents, increased SOD activity and GSH content, and upregulated SLC7A11 and GPX4 expression (P<0.05). Intraperitoneal injection of the SLC7A11 inhibitor produced the opposite result. CONCLUSION: Dexmedetomidine can protect intestine tissue from ischemia-reperfusion injury, which maybe correlates with activating SLC7A11 and inhibiting ferroptosis.

Key words: SLC7A11, ferroptosis, intestines, reperfusion injury, dexmedetomidine