Protective effect of anti-high mobility group box 1 on cerebral ischemia reperfusion injury in diabetic mice
10.3760/cma.j.issn.1671-8925.2016.09.006
- VernacularTitle:拮抗高迁移率族蛋白B1对糖尿病合并脑缺血再灌注损伤的保护作用研究
- Author:
Kai SUN
1
;
Xiuping ZHANG
;
Linjie SONG
;
Qingxia TAO
;
Chong WANG
Author Information
1. 潍坊医学院研究生处
- Keywords:
High mobility group box 1;
Cerebral ischemia-reperfusion injury;
Diabetes mellitus;
Inflammation reaction
- From:
Chinese Journal of Neuromedicine
2016;15(9):901-907
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether cerebral ischemia reperfusion (I/R) injury combined with diabetes mellitus (DM) could elevate concentrations of serum high mobility group box 1 (HMGB 1) and its related inflammatory factors,and to explore the underlying mechanism of cerebral I/R injury combined with DM by blocking HMGB 1.Methods One hundred and forty healthy male C57BL/6 mice were randomly divided into four groups:normoglycemia (NG) group (n=25),NG+I/R group (n=25),hyperglycemia (HG) group (n=25),and HG+I/R group (n=65);40 mice in the HG+I/R group were chosen and divided into anti-HMGB1 group and IgG control group (n=20).High-fat feeding and i.p.injection of streptozotocin were used to establish HG mouse models,and then,middle cerebral artery occlusion was performed to establish the HG+I/R mouse models.Mice were treated with tail intravenous injection of 30 μg/g anti-HMGB 1 polyclonal antibody or control IgG 1 h before ischemia as previously described.After accomplishment of animal models,serum HMGB1 concentrations were evaluated by ELISA,the permeability of blood brain barrier (BBB) was observed by Evans-blue fluorescence quantitative method,quantitative real-time PCR was introduced to detect the mRNA expressions of interleukin (IL)-1β,IL-6,and inducible nitric oxide synthase (iNOS).Morphology changes of damaged brains were observed by HE staining.Results The serum HMGB 1 level in the HG+I/R group was significantly higher than that in the NG+I/R group (P＜0.05).HG+I/R group had significantly higher BBB permeability than NG+I/R group (P＜0.05),while anti-HMGB1 group had significantly lower BBB permeability than HG+I/R group (P＜0.05).As compared with the NG group,the HG+I/R group had unclear cellular structures in the brain tissues with necrosis neurocytes and interstitial edema,while the cellular structures were obviously improved in the anti-HMGB1 group.Expressions ofIL-1β,IL-6 and iNOS in the HG+I/R group were significantly elevated as compared with those in the NG+I/R group (P＜0.05),while those in the anti-HMGBl group had significantly decreased levels ofIL-1β and iNOS as compared with those in the HG+I/R group (P＜0.05),and the IL-6 level showed no significant difference between the two groups (P＜0.05).Conclusion The pathogenesis of DM could increase concentration of serum HMGB 1,and anti-HMGB 1 mAb could alleviate brain injury by blocking HMGB 1,and render a new promising therapeutic way for DM patients suffered with ischemic stroke.
