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淀粉样肽对阿尔茨海默病大鼠模型记忆和中枢胰岛素抵抗的影响。

Effect of amylin on memory and central insulin resistance in a rat model of Alzheimer's disease.

机构信息

Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

出版信息

Arch Physiol Biochem. 2020 Oct;126(4):326-334. doi: 10.1080/13813455.2018.1534244. Epub 2018 Nov 17.

Abstract

Alzheimer's disease is strongly associated with brain insulin signalling. Investigating the effect of amylin as a novel treatment in streptozotocin (STZ) rat model of AD. Alzheimer's disease (AD) was induced in albino rats by intracerebroventricular injection of STZ (3 mg/kg). Rats received either amylin analogue (Pramlintide 200 μg/kg/day) or Metformin (30 mg/kg/day) for 5 weeks. Both Pramlintide and Metformin improve learning and memory through enhancing insulin signalling (p-IR and p-PI3K) which lead to lowering level of CSF glucose, phosphorylated tau proteins, and amyloid-β peptide (Aβ) in hippocampus. Insulin sensitisers as Metformin and Pramlintide can improve learning and memory and decrease the pathological changes in STZ induced rat model of AD. However, Pramlintide is superior to Metformin in some memory tests which related to its action as an amylin analogue. Amylin improves learning and memory through an independent effect other than insulin sensitisation.

摘要

阿尔茨海默病与大脑胰岛素信号密切相关。研究淀粉样肽作为 AD 型 STZ 大鼠模型的新型治疗方法的效果。通过向白化大鼠脑室内注射链脲佐菌素(STZ)(3mg/kg)诱导阿尔茨海默病(AD)。大鼠接受淀粉样肽类似物(普兰林肽 200μg/kg/天)或二甲双胍(30mg/kg/天)治疗 5 周。普兰林肽和二甲双胍都通过增强胰岛素信号(p-IR 和 p-PI3K)改善学习和记忆,从而降低海马体中 CSF 葡萄糖、磷酸化 tau 蛋白和淀粉样β肽(Aβ)的水平。胰岛素增敏剂如二甲双胍和普兰林肽可改善学习和记忆,并减少 STZ 诱导的 AD 大鼠模型中的病理变化。然而,普兰林肽在一些与胰岛素增敏作用无关的记忆测试中优于二甲双胍。淀粉样肽通过独立于胰岛素增敏的作用改善学习和记忆。

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