Role of histone deacetylase in sodium butyrate-induced reduction of intestinal ischemia-reperfusion injury in mice: relationship with oxidative stress and cell apoptosis / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of histone deacetylase (HDAC) in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with oxidative stress and cell apoptosis.Methods:Twenty-four SPF healthy male C57BL mice, aged 6-8 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) according to the random number table method: sham operation group (S group), intestinal I/R group (IR group), intestinal I/R+ sodium butyrate group (IN group) and intestinal I/R+ ITSA-1+ sodium butyrate group (INI group). In IR, IN and INI groups, the superior mesenteric artery was clamped for 45 min, followed by reperfusion for 2 h to prepare the model of intestinal I/R injury, while the superior mesenteric artery was only isolated without ligation in S group.One week before preparation of the model, sodium butyrate 500 mg/kg was intragastrically administered once a day in IN group and INI group, the HDAC activator ITSA-1 0.5 mg/kg was intraperitoneally injected three times a week in INI group, and the equal volume of normal saline was given instead in the other groups.The mice were sacrificed at 2 h of reperfusion and small intestinal tissues were obtained for microscopic examination of the pathological changes which were assessed using Chiu′s score and for determination of the content of MDA (by enzyme-linked immunosorbent assay) and expression of cleaved caspase-3 (by Western blot). Results:Compared with S group, Chiu′s score was significantly increased, and the expression of cleaved caspase-3 was up-regulated in IR, IN and INI groups, the content of MDA in small intestinal tissues was significantly increased in IR and INI groups ( P<0.05). Compared with IR group, Chiu′s score was significantly decreased in IN and INI groups, and the content of MDA was significantly decreased, and the expression of cleaved caspase-3 was down-regulated in IN group ( P<0.05). Compared with IN group, Chiu′s score and content of MDA were significantly increased, and the expression of cleaved caspase-3 was up-regulated in INI group ( P<0.05). Conclusions:HDAC is involved in sodium butyrate-induced reduction of intestinal I/R injury in mice, which is related to the inhibition of oxidative stress and cell apoptosis.