摘要
尽管环氧化酶2在神经退行性疾病抑制动物模型的神经保护作用,有最近的研究报导了有一些严重的副作用(溃疡,出血,致命的脑血管性疾病等)和环氧化酶2抑制剂的有限益处。一个更为中心的方法首先探索PGES-PGE2-EP信号通路变化以及米索前列醇对慢性铝过负荷大鼠神经退行性变的影响。灌胃处理的成年大鼠是葡萄糖酸铝管理。大鼠海马组织中PGE2内容与PGES 和EPs表达采用ELISA、q-PCR和Western blot分别分析。丙二醛(MDA)成分和超氧化物歧化酶(SOD)活性在大鼠海马区也有被探测。米索前列醇治疗剂量的依赖性改进的空间学习和记忆功能,为抵抗愈合后海马神经元损伤的慢性铝诱导的大鼠心肌细胞。同时,米索前列醇管理导致PGE2的水平降低和mPGES -1,EP2和EP4的表达水平的向下调节,但EP3有一个剂量独立性的上调表达。这些结果显示米索前列醇有神经保护性质,以及机制包括影响EP3的水平和减少PGE2通过负反馈机制内源性生产,提高在EP3中的表达水平,减少EP2和EP4的表达水平,和重建的mPGES-1-PGE2-EP1-4信号通路的平衡。在这种方式中,米索前列醇有效应对氧化应激和炎症的中枢神经系统。PGES-PGE2-EPs信号通路是一个对神经退行性疾病患者潜在的治疗策略。
关键词: 阿尔茨海默病,神经退行性变,米索前列醇,PGE2,PGES,EPs受体。
Current Alzheimer Research
Title:Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats
Volume: 13 Issue: 9
Author(s): Yuanxin Guo, Wenjuan Lei, Jianfeng Wang, Xinyue Hu, Yuling Wei, Chaonan Ji, Junqing Yang
Affiliation:
关键词: 阿尔茨海默病,神经退行性变,米索前列醇,PGE2,PGES,EPs受体。
摘要: Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE2-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels, while there was a dosedependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE2 through a negative feedback mechanism, increasing the EP3 expression level, decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients.
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Yuanxin Guo, Wenjuan Lei, Jianfeng Wang, Xinyue Hu, Yuling Wei, Chaonan Ji, Junqing Yang , Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats, Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205013666160401114601
DOI https://dx.doi.org/10.2174/1567205013666160401114601 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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