title: Glutamine decreases intestinal mucosal injury in a rat model of intestinal ischemia-reperfusion by downregulating HMGB1 and inflammatory cytokine expression.
abstract: Intestinal ischemia-reperfusion (IR) is a common clinical pathophysiological process that is common in severe trauma, major surgery, and in post-resuscitation. Glutamine (Gln) reduces intestinal IR injury, however, its mechanism of action remains to be determined. High mobility group box 1 (HMGB1) protein, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) are mediators involved in the pathophysiology of intestinal IR injury. The aim of the present study was to investigate the effects of Gln on the intestinal mucosa of HMGB1 expression following IR to determine whether Gln relieved intestinal IR injury in the intestinal mucosal barrier. Forty-eight Sprague-Dawley rats were included in the present study. A model of intestinal ischemia-reperfusion injury was established by clamping the superior mesenteric artery of the rats to cause ischemia, followed by restoring blood flow. The animals were randomly divided into the control (n=24) and the Gln (n=24) groups for the experiments. The two groups of rats were given enteral nutrition with equal heat, nitrogen (heat 125.4 kJ/kg/day, nitrogen 0.2 g/kg/day). The Gln group of rats was fed with enteral nutrition plus 3% Gln, while the control rats were fed with enteral nutrition plus 3% soybean protein. After 7 days, the HMGB1 and plasma levels of NF-κB, TNF-α, IL-1, Gln, D-lactic acid and diamine oxidase (DAO) were observed. The changes in the morphology of intestinal mucosa were observed using electron microscopy. The plasma levels of TNF-α, IL-1, D-lactic acid and DAO, and the level of HMGB1, NF-κB, TNF-α and IL-1 in intestinal mucosa were significantly higher after IR (p<0.05), while the plasma level of Gln was lower in the two groups. In the control group, the plasma level of IL-1, TNF-α, DAO and D-lactic acid, and that of HMGB1, NF-κB, TNF-α, and IL-1 in intestinal mucosa were significantly higher, while the plasma level of Gln was lower than that prior to modeling on the 3rd and 7th days of the experiment. In the Gln group, the plasma level of IL-1, TNF-α, DAO and D-lactic acid, and that of HMGB1, NF-κB, IL-1, and TNF-α in intestinal mucosa were significantly higher (p<0.05) compared to the control on the 3rd and 7th days of the experiment. By contrast, after the 7th day, the plasma level of IL-1, TNF-α, DAO and D-lactic acid, and the level of HMGB1, NF-κB, IL-1, TNF-α in intestinal mucosa were significantly lower in the Gln group, while the plasma level of Gln was significantly higher than those in control group and after IR on the 7th day of the experiment. Additionally, the structure of villi and recess was damaged, villi was sparse and short, and considerable inflammatory cell influx embellished the lamina propria, lymphangiectasia, and edema after IR. On the 7th day, compared to after IR, the intestinal villi and recess structure of the controls was significantly restored in the Gln group. In conclusion, Gln repaired the intestinal mucosal injury in IR by reducing the expression of HMGB1 and inflammatory cytokines, and reducing the permeability of the intestinal mucosa.
authors: Department of Nutrition, Jinshan Hospital, Fudan University School of Medicine, Shanghai 201508, P.R. China.
authors: Xiaoliang
authors: X
authors: Shu
authors: Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors: Jian
authors: J
authors: Zhang
authors: Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors: Qingxiu
authors: Q
authors: Wang
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors: Zengguang
authors: Z
authors: Xu
authors: Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors: Tingting
authors: T
authors: Yu
keywords: glutamine; high mobility group box 1; intestinal mucosa; ischemia-reperfusion; permeability