Glutamine ameliorates intestinal ischemia-reperfusion Injury in rats by activating the Nrf2/Are signaling pathway.

Ischemia-reperfusion (I/R)-mediated intestinal mucosal injury is usually induced by oxygen-derived toxic free radicals from the xanthine oxidase system after reperfusion, but the detailed molecular mechanisms underlying glutamine protection is still unclear. This study aims to elucidate whether glutamine prevents damage to the intestinal mucosa after I/R in rats and to investigate signaling by the Nrf2/ARE pathway induced by GLN in a rat model. Our results revealed that Glutamine pretreatment reduced jejunum injury and microvascular hyper-permeability induced by I/R. MDA level significantly increased while the SOD and GSH-Px levels decreased in the I/R group compared to the sham group and the GLN-I/R group. Both the mRNA and protein levels of the Nrf2 and HO-1 were significantly elevated by GLN pretreatment when compared to the I/R group. GLN treatment also elevated Bcl-2 levels, and accordingly suppressed apoptotic damage in the jejunum cells shown by decreased cleaved caspase-3 level. Mechanistic investigation revealed that GLN treatment augmented binding of Nrf2 onto Bcl2 gene promoter. These results indicate that glutamine has protective effects on I/R in vivo by activating the Nrf2/ARE signaling pathway to inhibit ROS production and reduce intestinal apoptosis.