Inhibition of NF-κB activity by aminoguanidine alleviates neuroinflammation induced by hyperglycemia
Inhibition of NF-κB activity by aminoguanidine alleviates neuroinflammation induced by hyperglycemia
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氨基胍抑制 NF-κ B 活性可减轻高血糖引起的神经炎症
DOI：
10.1007/s11011-017-0013-5
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发表时间：
2017-10-01
影响因子：
3.6
通讯作者：
Zhou, Xiaoyan
中科院分区：
文献类型：
--
作者：
Song, Yuanjian;Zhang, Fang;Zhou, Xiaoyan
神经炎症是糖尿病(DM)相关脑部并发症的一个重要特征。诱导型一氧化氮合酶(INOS)参与了神经炎症的发病机制。然而，iNOS如何促进脑部炎症的发生仍不清楚。本研究旨在探讨诱导型一氧化氮合酶(INOS)与糖尿病小鼠神经炎症的关系，并阐明iNOS选择性抑制剂氨基胍(AG)保护糖尿病小鼠神经元抗炎作用的可能机制。本实验采用单次注射链脲佐菌素(STZ)的方法建立糖尿病小鼠模型。糖尿病小鼠在疾病诱导后给予银杏叶提取物10周。检测血清和脑组织中iNOS活性，检测脑内胶质纤维酸性蛋白(GFAP)和离子钙结合蛋白-1(Iba-1)的表达。用免疫组织化学法和免疫印迹法检测胞浆和胞核中核因子-kappaB的表达。结果表明，AG可逆转血清和脑组织中iNOS的高表达。AG还可抑制GFAP和Iba-1的表达，抑制核转录因子-kappaB与胞浆内iNOS的结合，从而抑制核转位。结果表明，iNOS能在胞浆内与核因子-kappaB结合，促进其在糖尿病小鼠体内的核移植。此外，AG通过抑制iNOS活性而减轻神经炎症，并通过促进其与胞浆内iNOS的解离而减少核转录因子-kappaB的核转位。
Neuroinflammation is a key feature of cerebral complication which is associated with diabetes mellitus (DM). Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of neuroinflammation. However, how iNOS facilitates the development of inflammation in brain is still unidentified. The aim of the present study was to investigate the association of iNOS and neuroinflammation in diabetic mice, and elucidate the potential mechanisms underlying aminoguanidine (AG), the selective inhibitor of iNOS, protected neurons against inflammation in diabetic mice. In present experiment, diabetic mice model were established by a single intraperitoneal injection of streptozotocin (STZ). AG was administered to diabetic mice for ten weeks after this disease induction. Then we measured iNOS activity in the serum and brain, detected the glial fibrillary acidic protein (GFAP) and ionised calcium binding adaptor molecule-1 (Iba-1) expressions in the brain. Moreover, nuclear factor-kappa B (NF-kappa B) in cytoplasm and nucleus were tested by IP and WB. Results revealed that high expression of iNOS in serum and brain could be reversed by AG treatment. Furthermore, AG could also inhibit GFAP and Iba-1 expressions, and NF-kappa B nuclear translocation by inhibiting it from binding to iNOS in cytoplasm. Our findings indicated that iNOS can combine with NF-kappa B in cytoplasm and promote its nuclear transfer in diabetic mice. Furthermore, AG decreased neuroinflammation through inhibiting iNOS activity and reducing NF-kappa B nuclear translocation by promoting its dissociation with iNOS in cytoplasm.