The Role And Mechanism Of SIRT3 In Attenuation Of Intestinal Ischemia-reperfusion Injury By Dexmedetomidine In Mice

Objective: To explore the role and mechanism of silent mating type information regulator 2 homolog 3(SIRT3)in attenuation of intestinal ischemia-reperfusion(I/R)injury by dexmedetomidine in mice.Methods: Twenty-four healthy male C57 BL mice,were divided into 4 groups randomly(n=6): Sham operation group(Sham group),Intestinal ischemia-reperfusion group(I/R group),Dexmedetomidine group(Dex group),3-TYP group.Clamped of superior mesenteric artery for 45 min followed by reperfusion for 2h in I/R group,Dex group,and 3-TYP group for establishment of intestinal I/R model,while only did sham operation in Sham group.At 1h prior to onset of ischemia,injected 3-TYP into mice in3-TYP group intraperitoneally(5 mg/kg,diluted to 0.3ml),and 0.3ml normal saline into mice in Dex group intraperitoneally.At 30 min prior to onset of ischemia,injected dexmedetomidine into mice in 3-TYP group and Dex group intraperitoneally(25 μg/kg,diluted to 0.3ml).At both 1h and 30 min prior to onset of ischemia,injected 0.3ml normal saline into mice in Sham group and I/R group intraperitoneally,respectively.At2 h of reperfusion period,sacrificed the mice under anesthesia.Took intestinal tissues and observed pathological changes under light microscope after HE staining,and assessed injury score via the Chiu’s score method,and detected activity of SIRT3 and superoxide dismutase 2(SOD2),and malondialdehyde(MDA)level via spectrophotometry.Results: The pathological injury was exacerbated,and the Chiu’s score,the MDA level elevated remarkably,while the activity level of SIRT3 and SOD2 declined remarkably in I/R group,Dex group and 3-TYP group compared to Sham group(P<0.05).The pathological injury was alleviated,and the Chiu’s score declined remarkably in Dex group and 3-TYP group compared to I/R group(P<0.05);and the MDA level declined remarkably,while activity level of SIRT3 and SOD2 elevated remarkably in Dex group compared to I/R group(P<0.05);and there was no significant difference in the activity level of SIRT3 and SOD2 and the MDA level between 3-TYP group and I/R group.The pathological injury was exacerbated,and the Chiu’s score,the MDA level elevated remarkably,while the activity level of SIRT3 and SOD2 declined remarkably in 3-TYP group compared to Dex group(P<0.05).Conclusion: SIRT3 and its downstream SOD2 are involved in mediating the effect of attenuation of intestinal ischemia-reperfusion injury through inhibiting oxidative stress response by dexmedetomidine.