Deleterious Role of Anti-high Mobility Group Box 1 Monoclonal Antibody in Retinal Ischemia-reperfusion Injury
Deleterious Role of Anti-high Mobility Group Box 1 Monoclonal Antibody in Retinal Ischemia-reperfusion Injury
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DOI：
10.3109/02713683.2011.594201
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发表时间：
2010-04
影响因子：
2
通讯作者：
Shenyang Yang;K. Hirooka;Ye Liu;Tomoyoshi Fujita;Kouki Fukuda;Takehiro Nakamutra;T. Itano;Jiyong Zhang;M. Nishibori;F. Shiraga
中科院分区：
文献类型：
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作者：
Shenyang Yang;K. Hirooka;Ye Liu;Tomoyoshi Fujita;Kouki Fukuda;Takehiro Nakamutra;T. Itano;Jiyong Zhang;M. Nishibori;F. Shiraga
目的：目的探讨抗高迁移率族蛋白1（HMGB 1）单克隆抗体对大鼠视网膜缺血再灌注损伤的保护作用。材料与方法：视网膜缺血诱导增加，然后保持在130 mmHg的眼内压45分钟。腹腔注射抗HMGB 1单克隆抗体缺血前30分钟。在缺血后7天评价视网膜损伤。采用免疫组化和图像分析技术检测细胞内活性氧（ROS）水平的变化和抗HMGB 1单克隆抗体的定位。还进行了暗适应全视野视网膜电图（ERG）。结果：抗HMGB 1单克隆抗体预处理可明显加重视网膜缺血性损伤。视网膜缺血6-12 h HMGB 1表达增加。缺血后，视网膜细胞中检测到ROS的产生。然而，用抗HMGB 1 mAb预处理增加了ROS的产生。术后第7天，溶剂组的ERG a波和b波振幅均显著高于抗HMGB 1 mAb预处理组。结论：目前视网膜损伤的体内模型表明，抗HMGB 1 mAb在缺血-再灌注损伤中起着很大的有害作用。为了开发急性视网膜缺血性疾病的神经保护治疗策略，需要进一步研究抗HMGB 1 mAb的功能。
Purpose: To investigate the effect of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) against ischemia-reperfusion injury in the rat retina. Materials and Methods: Retinal ischemia was induced by increasing and then maintaining intraocular pressure at 130 mmHg for 45 min. An intraperitoneal injection of anti-HMGB1 mAb was administered 30 min before ischemia. Retinal damage was evaluated at 7 days after the ischemia. Immunohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of anti-HMGB1 mAb. Dark-adapted full-field electroretinography (ERG) was also performed. Results: Pretreatment with anti-HMGB1 mAb significantly enhanced the ischemic injury of the retina. HMGB1 expression increased at 6–12 h after ischemia in the retina. After the ischemia, production of ROS was detected in retinal cells. However, pretreatment with anti-HMGB1 mAb increased the production of ROS. On the seventh postoperative day, the amplitudes of both the ERG a- and b-waves were significantly higher in the vehicle group than in the groups pretreated with anti-HMGB1 mAb. Conclusions: The current in vivo model of retinal injury demonstrated that anti-HMGB1 mAb plays a large deleterious role in ischemia-reperfusion injury. In order to develop neuroprotective therapeutic strategies for acute retinal ischemic disorders, further studies on anti-HMGB1 mAb function are needed.