HMGB1介导急性高血糖对脑缺血大鼠血-脑脊液屏障的损伤  

Acute hyperglycemia w orsens ischemic stroke-induced blood-brain barrier impairment via HM GB1 in rats

作　　者：黄景阳[1] 杨承慧[1] 马坤润[1] 刘曦[1] 王逸飞[1] 陈海丽[1] 刘宝义[2] 袁中瑞[1] 

机构地区：[1]山东大学医学院病理生理学教研室,济南250012 [2]山东大学齐鲁医院呼吸内科,济南250012

出　　处：《山东大学学报（医学版）》2013年第9期17-21,共5页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金(2009ZRB01125);国家自然科学基金(81171106);中国博士后科学基金(20110491578);山东省博士后创新项目专项资金(201102016)

摘　　要：目的探讨急性高血糖对脑缺血大鼠血-脑脊液屏障(BBB)损伤的作用及机制。方法实验大鼠随机分为假手术组、正常血糖(NG)组、加甘草酸(GL)(NG+GL)组、高血糖(HG)组和加GL(HG+GL)组。于脑缺血再灌注不同时间段检测脑脊液高迁移率族蛋白B1(HMGB1)含量、BBB通透性、脑水肿和脑梗死体积,评估神经缺失。结果与NG组比较,HG组大鼠的脑脊液HMGB1含量显著提高(P<0.01);同时,伊文思蓝(EB)外渗率,脑梗死体积及脑水肿显著加重(P<0.01),神经功能缺陷加重(P<0.05);进行GL干预后,上述指标显著改善(P<0.01)。结论高血糖可促进缺血脑组织HMGB1的释放,加重BBB损伤。抑制HMGB1的活性,对高血糖大鼠脑缺血后BBB的损伤具有保护作用。Objective To investigate the effects of acute hyperglycemia on ischemia-induced blood-brain barrier （BBB） impairment and the mechanism involved. Methods Wistar rats were randomly divided into sham operation group, normoglycemia （NG） group, hyperglycemia （HG） group and glycyrrhizic acid （GL） intervention （ NG ＋ GL, HG ＋ GL） groups. Ischemia was induced by 90 minutes middle cerebral artery occlusion. Western blotting was used to detect the release of high mobility group box 1 （ HMGB1 ） in cerebrospinal fluid, and BBB permeability was evaluated by Evan＇s blue （EB） leakage. Brain edema, infarction volume, neurological deficit scores were evaluated after opera- tion. Results Hyperglycemia significantly enhanced the release of HMGB1 in cerebrospinal fluid, compared with the NG group （ P 〈 0.01 ）. Meanwhile, Hyperglycemia significantly increased the brain edema and the infarction volume （ P 〈 0.01 ） and worsened the neurological deficit （ P 〈 0.05 ）. Inhibition of HMGB1 with GL significantly reduced EB leakage, brain edema, infarction volume, and neurological deficit （P 〈 0.01 ）. Conclusion In transient middle cere- bral artery occlusion, the increased release of HMGB1 may contribute to the hyperglycemia-exacerbated BBB damage. Inhibiting HMGB1 may protect the BBB from the hyperglycemia-exacerbated damage.

关 键 词：高迁移率族蛋白B1 血-脑脊液屏障 甘草酸 脑缺血 大鼠 

分 类 号：R614.2[医药卫生—麻醉学] R332[医药卫生—外科学]