Role of Nrf2/HO-1 signaling pathway in atorvastatin-induced reduction of intestinal ischemia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of nuclear factor NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in atorvastatin-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divide into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (I/R group), atorvastatin group (ATV group) and atorvastatin+ Nrf2 inhibitor ML385 group (AM group). Intestinal I/R was produced by occlusion of superior mesenteric artery for 45 min followed by reperfusion.In ATV and AM groups, atorvastatin 10 mg/kg was given by gavage for 3 consecutive days daily at 3 day before establishment of the model, while the equal volume of normal saline was given by gavage in S and I/R groups.Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before establishment of the model in group AM.The mice were sacrificed at 2 h of reperfusion, and intestine tissues were obtained for examination of the pathological changes of intestinal tissues (with a light microscope) which were scored according to Chiu, for determination of wet/dry weight ratio (W/D ratio), for detection of the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) (by xanthine oxidase method and thiobarbituric acid condensation method) and for determination of the expression of Nrf2 and HO-1 (by Western blot). Results:Compared with S group, the Chiu score, W/D ratio and MDA content were significantly increased, the activity of SOD was decreased, and the expression of Nrf2 and HO-1 was up-regulated in the other 3 groups ( P<0.05). Compared with the group I/R, the Chiu score, W/D ratio and MDA content were significantly decreased, the SOD activity was increased, and the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological changes were significantly attenuated in group ATV, and no significant change was found in the parameters mentioned above in AM group ( P>0.05). Compared with the group ATV, the Chiu score, W/D ratio and MDA content were significantly increased, the SOD activity was decreased, the expression of Nrf2 and HO-1 was decreased ( P<0.05), and the pathological changes were significantly aggravated in group AM. Conclusion:The mechanism by which atorvastatin reduces intestinal I/R injury is related to activating Nrf2/HO-1 signaling pathway in mice.