Role of SIRT3∕FOXO3α signaling pathway in dexmedetomidine-induced reduction of hepatic ische-mia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of sirtuin 3 ( SIRT3)∕forkhead box O3α ( FOXO3α) signaling pathway in dexmedetomidine-induced reduction of hepatic ischemia-reperfusion ( I∕R) injury in mice. Methods Forty clean-grade C57BL∕6 mice of both sexes, aged 2 weeks, weighing 6-8 g, were di-vided into 4 groups (n＝10 each) using a random number table method: sham operation group (group S), hepatic I∕R group ( group I∕R), dexmedetomidine group ( group D) and SIRT3 inhibitor 3-TYP plus dexmedetomidine group (group T+D). Portal vein and hepatic artery supplying left and middle lobes of the liver and biliary tract were clamped resulting in ischemia of 70% of the liver in anesthetized rats. Normal sa-line 0. 25 ml was intraperitoneally injected at 1 h before establishing model, and 30 min later dexmedetomi-dine 50 μg∕kg (diluted to 0. 25 ml in normal saline) was intraperitoneally injected in group D. In group T+D, 3-TYP 5 mg∕kg (diluted to 0. 25 ml in normal saline) was intraperitoneally injected at 1 h before estab-lishing model, and 30 min later dexmedetomidine 50 μg∕kg (diluted to 0. 25 ml in normal saline) was in-traperitoneally injected. Mice were selected at 6 h after reperfusion, blood samples were obtained through eyeball, and the mice were then sacrificed and kidneys were removed for determination of the serum concen-trations of creatinine (Cr) and blood urea nitrogen (BUN), cell apoptosis (by TUNEL), malondialdehyde (MDA) content (using thiobarbituric acid method), superoxide dismutase (SOD) activity (by xanthine oxidase method), and acetylation of FOXO3α in renal tissues (by using immunoprecipitation) and for ex-amination of the pathologic changes. The damage to renal tubules was scored. Apoptosis index ( AI) was calculated. Results Compared with group S, the renal tubular damage score and AI were significantly in-creased, serum concentrations of Cr and BUN were increased, the content of MDA was increased, the ac-tivity of SOD was decreased, and the acetylation of FOXO3α was decreased in I∕R, D and T+D groups ( P＜0. 05). Compared with group I∕R, the renal tubular damage score and AI were significantly decreased, serum concentrations of Cr and BUN were decreased, the content of MDA was decreased, the activity of SOD was increased, and the acetylation of FOXO3α was decreased in group D (P＜0. 05), and no signifi-cant change was found in the parameters mentioned above in group T+D (P＞0. 05). Compared with group D, the renal tubular damage score and AI were significantly increased, serum concentrations of Cr and BUN were increased, the content of MDA was increased, the activity of SOD was decreased, and the acetylation of FOXO3α was decreased in group T+D ( P＜0. 05). Conclusion Activation of SIRT3∕FOXO3α signaling pathway is involved in dexmedetomidine-induced reduction of hepatic I∕R injury in mice.