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Methylated arginine analogues: their potential role in atherosclerosis and cognition using the poloxamer-407-induced mouse model of dyslipidemia

机译:甲基化精氨酸类似物:使用泊洛沙姆407诱导的血脂异常小鼠模型在动脉粥样硬化和认知中的潜在作用

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An experimental mouse model of dyslipidemia and atherosclerosis was utilized to study the generation of methylarginines in vivo, as well as any potential behavioral changes in mice associated with the production of excess methylarginines. Following 14 weeks of poloxamer 407 treatment, mice developed atherosclerosis and the plasma concentrations of monomethylarginine and asymmetric dimethylarginine were found to be significantly greater than corresponding concentrations in control mice. This finding may have contributed to the development of aortic atherosclerotic lesions in poloxamer-treated mice by interfering with nitric oxide availability and, hence, normal function of vascular endothelium. Poloxamer-407-treated mice also showed a significant decrease in locomotor and exploratory activity, together with signs of emotional stress and anxiety relative to controls. Passive avoidance testing to assess learning and memory provided suggestive evidence that poloxamer-treated mice could potentially be characterized as having undergone a disruption in the process of forgetting about an aversive event, specifically, a foot shock, when compared with control mice. Thus, it is also suggested that the increase in both plasma monomethylarginine and asymmetric dimethylarginine in poloxamer-407-treated mice may somehow influence learning and memory, because endothelial dysfunction caused by reduced nitric oxide availability has been hypothesized to negatively influence cognitive function.
机译:使用血脂异常和动脉粥样硬化的实验小鼠模型来研究体内甲基精氨酸的产生,以及与过量甲基精氨酸产生相关的小鼠任何潜在的行为变化。泊洛沙姆407治疗14周后,小鼠发展为动脉粥样硬化,单甲基精氨酸和不对称二甲基精氨酸的血浆浓度明显高于对照组小鼠的相应浓度。该发现可能通过干扰一氧化氮的可利用性并因此干扰了血管内皮的正常功能,促成了在泊洛沙姆治疗的小鼠中主动脉粥样硬化病变的发展。相对于对照组,用Poloxamer-407治疗的小鼠的运动和探索活动也显着降低,并且伴有情绪应激和焦虑的迹象。被动回避测试以评估学习和记忆能力,为暗示性证据提供了证据,表明与对照小鼠相比,泊洛沙姆治疗的小鼠在忘记厌恶事件(尤其是足部震颤)的过程中可能遭受了破坏。因此,也有人认为在泊洛沙姆407处理的小鼠中血浆单甲基精氨酸和不对称二甲基精氨酸的增加都可能以某种方式影响学习和记忆,因为已经假设一氧化氮利用率降低引起的内皮功能障碍会对认知功能产生负面影响。

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