胰高血糖素样肽-1 类似物可改善铝诱导痴呆大鼠的神经元和行为损伤，并促进神经保护。

Glucagon-like peptide-1 analog improves neuronal and behavioral impairment and promotes neuroprotection in a rat model of aluminum-induced dementia.

机构信息

Physiology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.

Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Egypt.

出版信息

Physiol Rep. 2021 Jan;8(24):e14651. doi: 10.14814/phy2.14651.

BACKGROUND

Alzheimer's disease (AD) is a worldwide severe medical and social burden. Liraglutide (LIR) has neuroprotective effects in preclinical animal models.

AIM

To explore the probable neuroprotective impact of Glucagon-like peptide-1 (GLP-1) on rats' behavior and to elucidate its underlying mechanisms.

METHODS

A total of 24 male albino rats were assigned to control, LIR (300 µg/kg subcutaneously (s.c.)), AD only (100 mg/kg aluminum chloride (AlCl ) orally) and LIR + AD treated groups. Eight radial arm maze was performed. Serum blood glucose, proinflammatory cytokines, oxidative stress markers were measured and hippocampal tissue homogenate neurotransmitters were evaluated. Histopathological and immunofluorescent examinations were performed.

RESULTS

LIR prevents the impairment of learning and improves both working memory and reference memory through significant reduction of serum tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon-γ (INF-γ) and malondialdehyde (MDA) and through the increase of superoxide dismutase (SOD), dopamine, adrenaline, and noradrenaline. LIR also improves hippocampal histological features of ALCL administrated rats and decreases the percentage of neuronal loss.

CONCLUSION

LIR normalizes ALCL -induced dementia. It improves cognitive dysfunction and ameliorates cerebral damage.

背景

阿尔茨海默病（AD）是一种全球性的严重医学和社会负担。利拉鲁肽（LIR）在临床前动物模型中具有神经保护作用。

目的

探讨胰高血糖素样肽-1（GLP-1）对大鼠行为的可能神经保护作用，并阐明其潜在机制。

方法

将 24 只雄性白化大鼠分为对照组、LIR（300µg/kg 皮下（s.c.））、AD 组（100mg/kg 氯化铝（AlCl ）口服）和 LIR+AD 治疗组。进行了 8 次放射臂迷宫实验。测量血清血糖、促炎细胞因子、氧化应激标志物，并评估海马组织匀浆神经递质。进行了组织病理学和免疫荧光检查。

结果

LIR 通过显著降低血清肿瘤坏死因子（TNF-α）、白细胞介素 6（IL-6）和干扰素-γ（INF-γ）和丙二醛（MDA），同时增加超氧化物歧化酶（SOD）、多巴胺、肾上腺素和去甲肾上腺素，预防学习障碍，并改善工作记忆和参考记忆。LIR 还改善了 ADCL 给药大鼠的海马组织学特征，并降低了神经元丢失的百分比。