Nicotine Inhibits Microglial Proliferation and Is Neuroprotective in Global Ischemia Rats
Nicotine Inhibits Microglial Proliferation and Is Neuroprotective in Global Ischemia Rats
复制标题
尼古丁抑制小胶质细胞增殖并对全身缺血大鼠具有神经保护作用
DOI：
10.1007/s12035-014-8825-3
复制
发表时间：
2015-06-01
影响因子：
5.1
通讯作者：
Gao, Tian-Ming
中科院分区：
文献类型：
--
作者：
Guan, Yan-Zhong;Jin, Xiu-Dong;Gao, Tian-Ming
啮齿动物模型中的缺血性损伤可靠地导致小胶质细胞的激活，这可能在神经元存活中起有害作用。我们的初步研究表明，尼古丁在减少体外培养的小胶质细胞的数量中起着潜在的作用。在本研究中，我们发现，缺血后2，6和12小时的尼古丁治疗7天显着增加缺血/再灌注大鼠的CA 1锥体神经元的存活。这种效应伴随着小胶质细胞而不是星形胶质细胞的增加显着减少，以及缺血/再灌注诱导的CA 1中肿瘤坏死因子-α（TNF-alpha）和白细胞介素-1 β（IL-1 β）的增强表达显着减少。尼古丁在有和没有粒细胞-巨噬细胞集落刺激因子（GM-CSF）刺激的原代培养物中抑制小胶质细胞增殖。用α-银环蛇毒素（一种选择性α 7烟碱乙酰胆碱受体（α 7 nAChR）拮抗剂）预处理可以防止尼古丁对培养的小胶质细胞增殖的抑制作用，表明尼古丁以α 7 nAChR依赖的方式抑制小胶质细胞增殖。我们的研究结果表明，尼古丁通过α 7 nAChR抑制小胶质细胞介导的炎症，并对缺血性卒中具有神经保护作用，即使在损伤后12小时给药。α 7 nAChR激动剂可用作人类的抗缺血化合物。
Ischemic injury in rodent models reliably leads to the activation of microglia, which might play a detrimental role in neuronal survival. Our preliminary studies suggest that nicotine plays a potential role in decreasing the numbers of cultured microglia in vitro. In the present study, we found treatment with nicotine 2, 6, and 12 h after ischemia for 7 days significantly increased the survival of CA1 pyramidal neurons in ischemia/reperfusion rats. This effect was accompanied by a significant reduction in the increase of microglia rather than astrocytes, as well as a significant reduction of enhanced expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1 beta) in CA1 induced by ischemia/reperfusion. Nicotine inhibits microglial proliferation in primary cultures with and without the stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF). Pre-treatment with alpha-bungarotoxin, a selective alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) antagonist, could prevent the inhibitory effects of nicotine on cultured microglial proliferation suggesting that nicotine inhibits the microglial proliferation in an alpha 7 nAChR-dependent fashion. Our results suggest that nicotine inhibits the inflammation mediated by microglia via alpha 7 nAChR and is neuroprotective against ischemic stroke, even when administered 12 h after the insult. alpha 7 nAChR agonists may have uses as anti-ischemic compounds in humans.