Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion
Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion
复制标题
腺苷 A1 受体调节 mTOR 信号传导以调节慢性脑灌注不足引起的白质炎症病变。
DOI：
10.1007/s11064-016-2056-0
复制
发表时间：
2016-12-01
影响因子：
4.4
通讯作者：
Xie, Peng
中科院分区：
文献类型：
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作者：
Cheng, Pengfei;Zuo, Xuzheng;Xie, Peng
我们试图研究腺苷 A1 受体 (A1AR) 在慢性脑灌注不足 (CCH) 下白质病变中的作用，并通过激活受体来探索潜在的修复机制。采用右侧单侧颈总动脉闭塞（rUCCAO）方法构建CCH模型。 2-氯-N6-环戊基腺苷 (CCPA) 是 A1AR 的特异性激动剂，用于探索 CCH 下白质病变修复的生物学机制。采用Western-blot检测哺乳动物雷帕霉素靶点（mTOR）、mTOR磷酸化（P-mTOR）、髓鞘碱性蛋白（MBP，白质髓鞘化标志物）的表达。通过 ELISA 测定促炎细胞因子肿瘤坏死因子-α (TNF-α) 和抗炎细胞因子白介素-10 (IL-10) 水平。与第2周、第4周和第6周的对照组相比，CCPA治疗组的P-mTOR/mTOR比值、MBP和IL-10的表达在第6周显着增加，而TNF-α的表达减少。 总之，A1ARs似乎通过mTOR信号通路减轻了rUCCAO小鼠白质的炎症。因此，A1ARs可以作为CCH下白质病变修复过程中的治疗靶点。
We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot. Pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and anti-inflammatory cytokine interleukin-10 (IL-10) levels were determined by ELISA. Compared with the control groups on week 2, 4 and 6, in CCPA-treated groups, the ratio of P-mTOR/mTOR, expression of MBP and IL-10 increased markedly, while the expression of TNF-alpha reduced at week 6. In conclusion, A1ARs appears to reduce inflammation in white matter via the mTOR signaling pathway in the rUCCAO mice. Therefore, A1ARs may serve as a therapeutic target during the repair of white matter lesions under CCH.