LIPOXIN A4 METHYL ESTER ALLEVIATES VASCULAR COGNITION IMPAIRMENT BY REGULATING THE EXPRESSION OF PROTEINS RELATED TO AUTOPHAGY AND ER STRESS IN THE RAT HIPPOCAMPUS
LIPOXIN A4 METHYL ESTER ALLEVIATES VASCULAR COGNITION IMPAIRMENT BY REGULATING THE EXPRESSION OF PROTEINS RELATED TO AUTOPHAGY AND ER STRESS IN THE RAT HIPPOCAMPUS
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DOI：
10.1515/cmble-2015-0027
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发表时间：
2015-09-01
影响因子：
8.3
通讯作者：
Lv, Peiyuan
中科院分区：
文献类型：
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作者：
Jia, Yanqiu;Jin, Wei;Lv, Peiyuan
由于自噬和内质网应激机制参与了一些神经退行性疾病和脑血管疾病，我们怀疑类似的机制可能参与慢性脑灌注不足引起的血管性认知障碍。脂氧素A（4）甲酯（LXA（4）ME）是一种炎症抑制剂，在实验性中风模型中表现出有效的保护作用。在早期的研究中，我们发现LXA（4）ME改善了使用双侧颈总动脉结扎（BCCAL）和双血管闭塞（2 VO）建立的血管性认知障碍大鼠模型的认知缺陷。在本研究中，LXA（4）ME治疗2 VO大鼠改善脑形态学缺陷。我们发现LXA（4）ME降低了2 VO大鼠海马中一些自噬和ERS相关因子的表达，即C/EBP同源蛋白、beclin 1和微管相关蛋白轻链3 II（LC 3-II）与LC 3-I的比值。LXA（4）ME可上调磷酸化mTOR、总mTOR、葡萄糖调节蛋白78、剪接和未剪接的X-box结合蛋白-1mRNA的蛋白表达。LXA（4）ME对蛋白质的差异调节可能是其保护慢性脑低灌注后认知功能的基础。
Since autophagy and endoplasmic reticulum stress mechanisms are involved in some neurodegenerative and cerebral vascular diseases, we suspected that similar mechanisms might participate in vascular cognitive impairments induced by chronic cerebral hypoperfusion. Lipoxin A(4) methyl ester (LXA(4) ME) is an inflammation inhibitor that exhibits potent protective effects in experimental stroke models. In an earlier study, we found that LXA(4) ME improved cognitive deficit in a rat model of vascular cognitive impairment created using bilateral common carotid artery ligation (BCCAL) and two-vessel occlusion (2VO). In this study, LXA(4) ME treatment of 2VO rats improved brain morphological defects. We found that LXA(4) ME reduced the expression of some autophagy-and ERS-related factors in the hippocampus of 2VO rats, namely C/EBP homologous protein, beclin1 and the ratio of microtubule-associated protein light chain 3 II (LC3-II) to LC3-I. By contrast, LXA(4) ME upregulated the protein expression of phospho-mTOR, total-mTOR, glucose-regulated protein 78 and spliced and unspliced X-box binding protein-1 mRNA. Differential protein regulation by LXA(4) ME might underlie its ability to protect cognition after chronic cerebral hypoperfusion.