Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
J Surg Res. 2012 Nov;178(1):466-71. doi: 10.1016/j.jss.2012.01.044. Epub 2012 Apr 1.
High mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxic shock and sepsis. The purpose of the present study was to investigate the role of HMGB1 in response to ischemia-reperfusion injury.
Ischemia-reperfusion injury was induced in male Wistar rats by clamping the superior mesenteric artery for 60 min. Using this model, the serum concentrations and localization of HMGB1 were investigated. The histologic findings from reperfused intestines and the survival rates were compared between the anti-HMGB1 antibody treatment groups (group A treated with 6.0 mg/kg antibody and group B with 0.6 mg/kg antibody) and the control antibody treatment group (control group).
Serum HMGB1 concentrations increased early after reperfusion and peaked at 3 h. Immunohistochemistry for HMGB1 revealed a high degree of positive staining in the epithelial cells of the damaged villi. Anti-HMGB1 antibody treatment significantly reduced this damage (P < 0.05) and improved the 48-h survival rate (90% in group A versus 50% in the controls; P < 0.05).
These results suggest that HMGB1 plays a key role in small intestinal ischemia-reperfusion injury.
高迁移率族蛋白 B1（HMGB1）最近被证明是内毒素休克和败血症的重要晚期介质。本研究的目的是研究 HMGB1 在缺血再灌注损伤中的作用。
雄性 Wistar 大鼠通过夹闭肠系膜上动脉 60 分钟来诱导缺血再灌注损伤。使用该模型，研究了 HMGB1 的血清浓度和定位。比较了抗 HMGB1 抗体治疗组（A 组给予 6.0mg/kg 抗体，B 组给予 0.6mg/kg 抗体）和对照抗体治疗组（对照组）的再灌注肠组织的组织学发现和存活率。
再灌注后早期血清 HMGB1 浓度升高，3 小时达到峰值。HMGB1 的免疫组化显示受损绒毛上皮细胞呈高度阳性染色。抗 HMGB1 抗体治疗显著减轻了这种损伤（P<0.05），并提高了 48 小时的存活率（A 组为 90%，对照组为 50%；P<0.05）。
这些结果表明 HMGB1 在小肠缺血再灌注损伤中起关键作用。
