D-4F increases microRNA-124a and reduces neuroinflammation in diabetic stroke rats.
D-4F increases microRNA-124a and reduces neuroinflammation in diabetic stroke rats.
复制标题
D-4F 增加糖尿病中风大鼠的 microRNA-124a 并减少神经炎症
DOI：
10.18632/oncotarget.20751
复制
发表时间：
2017-11-10
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Ning R;Venkat P;Chopp M;Zacharek A;Yan T;Cui X;Seyfried D;Chen J
D-4F是一种促进抗炎作用的载脂蛋白A1模拟肽。MicroRNA-124是含量最丰富的脑特异性microRNA，具有抗炎作用。本研究旨在探讨D-4F对1型糖尿病(T1 DM)大鼠卒中的治疗作用及其机制。雄性Wistar大鼠采用T1 DM模型，采用大脑中动脉闭塞模型，分别给予PBS或D-4F(1 mg/kg，ip)治疗。卒中后2、24、48h(n=8/组)。在体内和体外进行一系列功能测试、脑血屏障(BBB)完整性、脑白质变化和microRNA表达。D-4F治疗能显著改善T1 DM卒中大鼠的功能结局，减少血脑屏障渗漏，增加紧密连接蛋白表达，减少脑白质损伤和炎性因子表达，同时增加抗炎M2巨噬细胞极化。D-4F可显著增加缺血脑、原代培养的皮质神经元和小胶质细胞中microRNA-124a的表达，降低基质金属蛋白酶-9、肿瘤坏死因子-α和Toll样受体-4基因的表达。抑制原代培养的皮质神经元和小胶质细胞中的microRNA-124可减弱D-4F诱导的抗炎作用和M2巨噬细胞的极化。D-4F治疗T1 DM卒中可增加microRNA-124的表达，促进抗炎作用和M2巨噬细胞极化，这可能是D-4F改善神经功能、血脑屏障和脑白质完整性的机制之一。
D-4F is an apolipoprotein-A1 mimetic peptide that promotes anti-inflammatory effects. MicroRNA-124 is the most abundant brain-specific microRNA and has anti-inflammatory effects. In this study, we investigated the therapeutic efficacy and mechanisms of D-4F treatment of stroke in type one diabetes mellitus (T1DM) rats. Male Wistar rats were induced with T1DM, subjected to embolic middle cerebral artery occlusion and treated with PBS or D-4F (1 mg/kg i.p.) at 2, 24 and 48 hours after stroke (n=8/group). A battery of function tests, brain blood barrier (BBB) integrity, white matter changes and microRNA expression were evaluated in vivo and in vitro. D-4F treatment in T1DM-stroke rats significantly improves functional outcome, decreases BBB leakage, increases tight junction protein expression, decreases white matter damage and inflammatory factor expression, while increasing anti-inflammatory M2 macrophage polarization in the ischemic brain. D-4F significantly increases microRNA-124a expression, and decreases matrix metalloproteinase-9, tumor necrosis factor-α and toll-like receptor-4 gene expression in the ischemic brain, and in primary cortical neuronal and microglial cultures. Inhibition of microRNA-124 in cultured primary cortical neurons and microglia attenuates D-4F induced anti-inflammatory effects and M2 macrophage polarization. D-4F treatment of T1DM-stroke increases microRNA-124 expression, promotes anti-inflammatory effects and M2 macrophage polarization, which may contribute to D-4F-induced improvement in neurological function, and BBB and white matter integrity.
登录
查看更多内容
影响因子：
8.3
作者：
Fan X;Qiu J;Yu Z;Dai H;Singhal AB;Lo EH;Wang X
通讯作者：
Wang X
影响因子：
4.3
作者：
King, George L.
通讯作者：
King, George L.
影响因子：
37.8
作者：
Kruger, AL;Peterson, S;Abraham, NG
通讯作者：
Abraham, NG
DOI：
10.1097/nen.0b013e3181c3ce6c
发表时间：
2010-01-01
影响因子：
3.2
作者：
Moxon-Emre, Iska;Schlichter, Lyanne C.
通讯作者：
Schlichter, Lyanne C.
影响因子：
4.8
作者：
Fischer-Posovszky, Pamela;Wang, Qiong A.;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.