Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion.
Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion.
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DOI：
10.1155/2012/209794
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Kuang G;He Q;Zhang Y;Zhuang R;Xiang A;Jiang Q;Luo Y;Yang J
本研究旨在探讨过氧化物酶体增殖物激活受体-β（PPAR-β）激动剂GW 0742对大鼠全脑缺血再灌注损伤（GCIRI）的神经保护作用及其机制。GCIRI后大鼠出现记忆和认知障碍，海马神经元细胞形态学改变。GW 0742预处理可显著改善上述作用，且呈剂量依赖性。GCIRI后IL-1β、IL-6和TNF-α的表达增加，而GW 0742预处理可抑制GCIRI对这些促炎细胞因子的增加。同样，GW 0742预处理也改善了GCIRI诱导的IL-10表达的降低，IL-10可以作为抑制性细胞因子减轻脑缺血损伤。另一方面，全脑缺血再灌注后，海马神经元核转位明显，NF-κB p65表达明显增加，而GW 0742预处理可明显抑制这种现象。与GCIRI组相比，GCIRI + GW 0742组细胞中PPAR-β的mRNA和蛋白表达均显著降低。结果提示，GW 0742通过激活大鼠海马组织中的PPAR-β，抑制NF-κB的表达和激活，发挥抗炎作用，从而对GCIRI大鼠产生明显的神经保护作用。
The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-α were increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-β were significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-β agonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-β activation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus.
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影响因子：
3.6
作者：
Berry, EBE;Keelan, JA;Mitchell, MD
通讯作者：
Mitchell, MD
影响因子：
4.8
作者：
Iadecola, C;Alexander, M
通讯作者：
Alexander, M
DOI：
10.1124/jpet.106.115758
发表时间：
2007-03-01
影响因子：
3.5
作者：
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通讯作者：
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3.5
作者：
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通讯作者：
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影响因子：
4.7
作者：
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通讯作者：
Giannakopoulos, Panteleimon