Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation
Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation
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DOI：
10.1016/j.peptides.2014.09.016
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发表时间：
2015-01-01
期刊：
影响因子：
3
通讯作者：
Bai, Bo
中科院分区：
文献类型：
--
作者：
Xin, Qing;Cheng, Baohua;Bai, Bo
急性炎症反应在缺血后神经元损伤的病理过程中起重要作用。爱帕琳-13已经被研究为用于各种神经障碍的神经肽。本研究旨在探讨Apelin-13对脑缺血/再灌注（I/R）损伤炎症反应的影响。采用大鼠大脑中动脉阻塞（MCAO）2 h再灌注24 h的方法建立大鼠短暂局灶性脑缺血再灌注模型。然后，大鼠在缺血后再灌注开始时接受apelin-13或载体治疗。用TTC染色法测定脑梗死体积，并评价神经功能缺损程度。测定髓过氧化物酶（MPO）活性。使用实时PCR测量促炎细胞因子的表达，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1 β）和细胞间粘附分子-1（ICAM-1）。采用免疫组化和Western blot检测apelin受体（APJ）、钙离子结合适体分子-1（Iba 1）、胶质细胞酸性蛋白（GFAP）和高迁移率族蛋白B1（HMGB 1）的表达。我们的结果表明，在I/R大鼠中用爱帕琳-13治疗显著减少神经功能缺损和梗死体积。Apelin-13可抑制I/R诱导的MPO活性升高。实时荧光定量PCR结果显示，apelin-13可降低I/R大鼠IL-1 β、TNF-α和ICAM-1等炎性细胞因子的表达。I/R大鼠APJ表达增加。Apelin-13可降低I/R大鼠Iba 1、GFAP和HMGB 1的表达，抑制小胶质细胞、星形胶质细胞等炎性细胞的增殖。综上所述，apelin-13通过抑制神经炎症反应对神经元I/R具有保护作用。(C)2014爱思唯尔公司All rights reserved.
Acute inflammation plays an important role in the pathogenic progression of post-ischemic neuronal damage. Apelin-13 has been investigated as a neuropeptide for various neurological disorders. The present study was performed to evaluate the effects of apelin-13 on the inflammation of cerebral ischemia/ reperfusion (I/R) injury. Transient focal I/R model in male Wistar rats were induced by 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. Rats then received treatment with apelin-13 or vehicle after ischemia at the onset of reperfusion. The neurological deficit was evaluated and the infarct volume was measured by TTC staining. The activity of myeloperoxidase (MPO) was measured. The expression of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and intercellular adhesion molecule-1 (ICAM-1) were measured using real-time PCR. And the expression of apelin receptor (APJ), ionized calcium-binding adapter molecule-1 (Iba1), glial fibrillary acidic protein (GFAP) and high mobility group box 1 (HMGB1) were measured by immunohistochemistry and western blot. Our results demonstrated that treatment with apelin-13 in I/R rats markedly reduced neurological deficits and the infarct volume. The increase of MPO activity induced by I/R was inhibited by apelin-13 treatment. The real-time PCR showed that apelin-13 decreased the expression of inflammatory cytokines such as IL-1 beta, TNF-alpha and ICAM-1 in I/R rats. The expression of APJ in I/R rats was increased. And the expression of Iba1, GFAP and HMGB1 in I/R rats was decreased by apelin-13 treatment indicating the inhibition of microglia, astrocytes and other inflammatory cells. In conclusion, apelin-13 is neuroprotective for neurons against I/R through inhibiting the neuroinflammation. (C) 2014 Elsevier Inc. All rights reserved.