To Investigate Whether Glutamine Protects Against I/R Injury In Vivo And To Study The Mechanism In This Process

Background: Glutamine is the most important and the most likely to absorb of the energy fuels in intestinal epithelial cells, lymphocytes and macrophages. Glutamine is the precursors of glutathione and other important substances nucleotide synthesis in antioxidant defense system. This study aimed to investigate whether glutamine (GLN) protects against I/R injury in vivo and to study the role of the Nrf2/ARE signaling pathway in this process.Methods:Thirty male Wistar rats were randomly divided into three groups (n=10):the s ham group, I/R group, and GLN pretreatment+I/R group. GLN pretreatment group anima Is were orogastrically pretreated with 1 g/kg/d GLN for 7 days, and the other two groups were pretreated with normal saline in the same manner. Intestinal I/R was induced by a 30-min occlusion of the superior mesenteric artery followed by 24 h of reperfusion. Subse quently, the intestinal segment was removed for morphological scoring on a scale describe d by Chiu et al. The protein expression levels of Nrf2, HO-1, occludin were measured by histochemistry and mRNA levels wree measured by real-time PCR. Further, blood sampl es were drawn from the portal vein to determine endotoxin levels, serum D-lactic acid, m alondialdehyde(MDA), superoxide dismutase(SOD), and GSH-Px levels.Results:(1)After reperfusion, compared with the Sham group, I/R group of intestinal epithe lial missing, with glandular disorders, some fluff top bleeding, occludin protein levels w ere significantly decreased; GLN group showed mild subcutaneous space to expand the int estinal mucosa villi,villus edema,gland morphology was normal lamina propria edema,occlu din protein levels were significantly increased. D-lactic acid and plasma endotoxin levels o f I/R group were significantly increased compared with Sham group (P<0.05). These indi cated that the intestinal mucosal barrier dysfunction, intestinal permeability elevated, and th e endotoxemia emerged in the I/R; D-lactate and plasma endotoxin levels of GLN group were significantly lower than that of the Sham group (P<0.05). This indicated that gluta mine can protect the intestinal mucosa from damage, reduce the incidence of endotoxemi a. Glutamine can reduce the barrier function damage caused by ?/R.(2)After reperfusion, the level of serum MDA in I/R group is higher than that of Sha m group and GLN group, while, the serum SOD and GSH-Px levels of I/R group were 1 ower than that of Sham and GLN group. The Nrf-2, HO-1 protein and mRNA levels of I /R group and GLN group were significantly higher than that of Sham group.This indicate d that the protective effect of glutamine in intestinal ischemia-reperfusion injury might be inhibit of oxidative stress and activate Nrf2/ARE signaling pathway.Conclusions: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.