BONE MARROW STROMAL CELLS INHIBITS HMGB1-MEDIATED INFLAMMATION AFTER STROKE IN TYPE 2 DIABETIC RATS

BONE MARROW STROMAL CELLS INHIBITS HMGB1-MEDIATED INFLAMMATION AFTER STROKE IN TYPE 2 DIABETIC RATS
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骨髓基质细胞抑制 2 型糖尿病大鼠中风后 HMGB1 介导的炎症。

DOI:
10.1016/j.neuroscience.2016.02.058
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发表时间:
2016-06-02
期刊:
影响因子:
3.3
通讯作者:
Ye, X.
Ye, X.
中科院分区:
医学3区
文献类型:
--
作者:
Hu, J.;Liu, B.;Ye, X.

文献摘要

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高迁移率族蛋白1(HMGB 1)是糖基化终产物受体(receptor for advanced glycation endproducts,ERK)的配体,具有促炎作用。它主要参与炎症激活,并有助于中风的发生和发展。采用2型糖尿病大鼠短暂性大脑中动脉闭塞(MCAo)模型,研究脑卒中后促炎症介质、血脑屏障(BBB)通透性及功能转归的变化。与对照组相比,2型糖尿病大鼠脑卒中后病变体积没有增加,但HMGB 1和HMGB 2表达明显增加,血脑屏障渗漏明显增加,功能恢复明显减少。2型糖尿病大鼠注射骨髓基质干细胞(BMSCs)可显著降低HMGB 1和HMGB 2的表达,减少血脑屏障渗漏,改善脑卒中后的功能转归。BMSC治疗的2型糖尿病大鼠抑制炎症并改善卒中后的功能结局。此外,体外数据支持以下假设:BMSC诱导的T2 DM-MCAo大鼠中HMGB 1和HMGB 2的减少有助于减弱缺血性脑中的炎症反应,这可能导致BMSC治疗的有益作用。需要进一步研究BMSCs治疗2型糖尿病卒中。(C)2016年IBRO。由爱思唯尔有限公司出版。保留所有权利。
High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of proinflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats. Injection of bone marrow stromal cells (BMSCs) into type 2 diabetic rats significantly reduced the expression of HMGB1 and RAGE, attenuated BBB leakage, and improved functional outcome after stroke. BMSCs-treated type 2 diabetic rats inhibited inflammation and improved functional outcome after stroke. Furthermore, in vitro data support the hypothesis that BMSCs-induced reduction of HMGB1 and RAGE in T2DM-MCAo rats contributed to attenuated inflammatory response in the ischemic brain, which may lead to the beneficial effects of BMSCs treatment. Further investigation of BMSCs treatment in type 2 diabetic stroke is warranted. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.