Research of the role and its significance of HMGB1 in intestinal ischemia-reperfusion injury

Objective To investigate the role and its significance of high mobility group box chromosomal protein 1(HMGB1) in ischemia-reperfusion injury in the rat small intestine. Methods Normal male Sprague-Dawley rats[(280±20)g] were randomly divided into sham-operated group(A group, n=36), intestinal ischemia-reperfusion injury group(B group, n=36), and ischemia-reperfusion injury control group(C group, n= 36). A group was subjected to surgical manipulation without intestinal ischemia. B and C group were subjected to superior mesenteric artery occlusion for 60 minutes and reperfusion. In C group anti-HMGB1 antibody(200 μg/kg) were also administered intraperitoneally one hour before operation. Detecting the level of HMGB1 expression in serum and intestinal tissue 3, 6, 12, 24, 48 and 72 hours after reperfusion, and the damage degree of intestinal epithelium and the serum concentrations of TNF-α and IL-6 should also be measured. Results A small amount of HMGB1 could be expressed in normal mice, while it increased markedly in the mice treated with intestinal ischemia-reperfusion injury. HMGB1 concentrations increased 3h after reperfusion, peaked at 12h and then decreased. 72 h after reperfusion it almost returned to the level before ischemia. The variation trend of serum IL-6 and TNF-α level was approximately the same as HMGB1. After 3 h of reperfusion intestinal mucosal villus epithelial cells fell off completely, and the villi height was decreased obviously. After 6 h part of Lamina propria disrupted. At the 12 h intestinal villus epithelial cells on both sides shed into pieces. 24 h after reperfusion intestinal mucosa started to regenerate and be more obvious in the next 24 h. The villi height increased to nearly normal levels after 72 h. The expression of HMGB1, TNF-α and IL-6, and the small intestinal epithelium damage degree were significantly higher in B group than in C group(P0.05). Conclusions HMGB1 in intestinal ischemia-reperfusion increases markedly and the level of HMGB1 is directly bound up with intestinal injury degree, indicating that it plays a major role in intestinal ischemia-reperfusion injury. We suggest that HMGB1 level can be an important index in the prediction and evaluation of intestinal ischemia-reperfusion injury degree, and by inhibiting HMGB1expression we could open a new avenue for preventing intestinal ischemia-reperfusion injury.