Hu J, Liu B, Zhao Q, Jin P, Hua F, Zhang Z, Liu Y, Zan K, Cui G, Ye X
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China; Department of Geriatric Neurology, Nanjing Brain Hospital, Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China.
Neuroscience. 2016 Jun 2;324:11-9. doi: 10.1016/j.neuroscience.2016.02.058. Epub 2016 Mar 2.
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 pro-inflammation 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.
高迁移率族蛋白B1（HMGB1）是晚期糖基化终产物受体（RAGE）的配体，作为一种促炎因子发挥作用。它主要参与炎症激活，并促进中风的发生和发展。通过使用2型糖尿病大鼠短暂性大脑中动脉闭塞（MCAo）模型，我们研究了中风后促炎介质、血脑屏障（BBB）渗漏及功能结局的变化。与对照大鼠相比，2型糖尿病大鼠的梗死体积并未增加，但HMGB1和RAGE的表达显著增加，BBB渗漏增加，且中风后的功能结局较差。向2型糖尿病大鼠注射骨髓间充质干细胞（BMSC）可显著降低HMGB1和RAGE的表达，减轻BBB渗漏，并改善中风后的功能结局。经BMSC治疗的2型糖尿病大鼠可抑制炎症并改善中风后的功能结局。此外，体外实验数据支持以下假说：BMSC诱导T2DM-MCAo大鼠体内HMGB1和RAGE的减少有助于减轻缺血性脑内的炎症反应，这可能是BMSC治疗产生有益效果的原因。有必要对2型糖尿病性中风的BMSC治疗进行进一步研究。
