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葛根素激活胆碱能抗炎通路抗脑缺血再灌注后炎症反应实验研究.doc

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Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway Xiaojie Liu, Zhigang Mei, Jingping Qian, Yongbao Zeng, Mingzhi Wang Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China 窗体顶端 Abstract: Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral is-chemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi-ated through the activation of the cholinergic anti-inflammatory pathway. Key words: neural regeneration; cerebral ischemia/reperfusion; inflammation; cholinergic anti-inflammatory pathway; alpha7 nicotinic acetylcholine receptors; nuclear factor kappa B; janus-activated kinase 2; signal transducers and activators of transcription 3; grants-supported paper; neuroregeneration; 窗体底端 Acceptance date: 2013-08-24      Cite this article: Xiaojie Liu, Zhigang Mei, Jingping Qian, Yongbao Zeng, Mingzhi Wang. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway[J]. Neural Regeneration Research, 2013, 8(34): 3203-3215.
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