Ischemic Preconditioning Preventing Downregulation of miR-182 Protects Intestine Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis

Abstract

Intestinal ischemia/reperfusion (I/R) injury is a severe condition associated with high morbidity and mortality. Ischemic preconditioning (IPC) had been found to be the most promising strategies against I/R injury. However, the potential molecular mechanisms underlying the protective effect of IPC have not been fully disclosed. MicroRNA182 (miR-182) is closely related to apoptosis and plays an important role in I/R injury. Our recent study demonstrated that miR-182 was down-regulated in the intestinal mucosa after I/R injury. However, whether miR-182 is involved in the protective effects of IPC in the setting of intestinal I/R injury is unknown. To investigate the role of miR-182 in the protective effect of IPC in intestine after I/R injury and potential mechanisms. AntagomiR-182 was pretreated before IPC in mice with intestinal I/R injury. MiR-182 mimic was administered before oxygen and glucose deprivation and reperfusion (OGD/R) in mice intestinal mucosa epithelial (MIME) cells. IPC partially prevented the downregulation of miR-182 in mice, which was blocked by pretreatment with antagomiR-182. Compared with the IPC group, pretreatment with antagomiR-182 further increased Chiu's scores and diamine oxidase activities. Meanwhile, apoptotic cells and cleaved caspase-3 expression were increased. Compared with the OGD/R group, pretreatment with miR-182 mimic prevented the downregulation of miR-182, improved cell survival, reduced apoptosis and cleaved caspase-3 expression in MIME cells. The downregulation of miR-182 was partially prevented by IPC, which was involved in IPC induced intestinal protection, and the mechanisms may be associated with inhibition of apoptosis.