Necroptosis Involves in Mechanism of Lung Injury Induced by Intestinal Ischemia-Reperfusion / 中山大学学报(医学科学版)

ABSTRACT

[Objective] To explore whether necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion.[Method] Thirty-two healthy male Sprague-Dawley rats were randomly assigned into 4 groups (n--8)sham operation group (sham group),isehemia/ reperfusion group (I/R group),necroptosis inhibitor necrostatin-1 group (Nec-1 group) and solvent dimethyl sulfoxide (DMSO) group (DMSO group).Model of intestinal I/R injury was produced by clamping the superior mesenteric artery for 1.5 h followed by 6 h reperfusion in rats.Necrostatin-1 1.0 mg/kg was administered 30 min before occlusion in Nec1 group,while the equal volume of DMSO was given instead in DMSO group.The rats were sacrificed at 6 h of reperfusion and the lung tissues were removed for measurement of wet-dry ratio and microscopic examination and scored.The expression of receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3) in lung tissues was detected using Western-blot and immunohistochemistry.[Result] Compared with sham group,lung morphology score and wet/dry ratio in I/R,DMSO group raised (P ＜ 0.05).Lung morphology score and wet/dry ratio statistically declined in Nec-1 group compared with I/R and DMSO group (P ＜ 0.05),while there was no statistical difference of wet/dry ratio between sham group and Nec-1 group (P ＞ 0.05).As the result of westernblot and immunohistochemistry showed,the expression of RIP1 and RIP3 was up-regulated in I/R group and DMSO group (P ＜0.05),which was inhibited by Nec-1 in Nec-1 group (P ＜ 0.05).[Conclusion] Necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion,and Nec-1,the special inhibitor of RIP1,can reduce the injury.