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N-硬脂酰乙醇胺对老年大鼠具有心脏保护作用。

N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats.

机构信息

OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Leontovich Str, 9, Kyiv, 03160, Ukraine.

DF Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine, Vyshgorodska Str, 67, Kyiv, 04114, Ukraine.

出版信息

Curr Aging Sci. 2024;17(2):144-155. doi: 10.2174/0118746098275323231226073348.

DOI:10.2174/0118746098275323231226073348
PMID:38279735
Abstract

BACKGROUND

Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS. The results of different studies over the past decades have established the protective effect of NAE on many pathological conditions.

OBJECTIVE

This study aimed to investigate the cardioprotective effects of C18:0 NAE- N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE- N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues.

METHODS

The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis.

RESULTS

The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes.

CONCLUSION

The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.

摘要

背景

衰老与代谢过程减缓、生理过程减弱、激素活性变化以及氧化应激和慢性炎症因素的增加有关。内源性大麻素系统(ECS)是一个主要的信号网络,在人体中枢和外周器官中发挥着促进内稳态的作用。一类称为 N-酰基乙醇胺(NAE)的少量脂质,除了花生四烯酸乙醇胺(anandamide)之外,不激活大麻素受体,但可以增强内源性大麻素的作用,具有广泛的生物活性和显著的适应原潜力,属于 ECS。过去几十年的不同研究结果已经确定了 NAE 对许多病理状况的保护作用。

目的

本研究旨在研究 C18:0 NAE- N-硬脂酰乙醇胺(NSE)对老年大鼠的心脏保护作用。在这项研究中,我们专注于研究 C18:0 NAE- N-硬脂酰乙醇胺(NSE)对氧化/硝化应激强度、抗氧化潜力、血浆脂蛋白谱和炎症标志物、磷脂组成以及老年大鼠心脏组织的与年龄相关的形态变化的影响。

方法

该研究在 Sprague Dawley 雄性实验室大鼠上进行。三组大鼠参与了研究设计。第一组由 4 个月龄的年轻大鼠组成(n=10)。第二(n=10)和第三(n=10)组包括 18 个月龄的老年大鼠。第三组的大鼠每天口服给予 50mg/kg 体重的 NSE 水性混悬液,持续 10 天。所有大鼠均保持在标准的 vivarium 饮食中。大鼠的血浆、血清和心脏用于生化和组织学分析。

结果

在老年大鼠中,N-硬脂酰乙醇胺表现出心脏保护作用,表现在抗氧化系统状况和促炎细胞因子水平的正常化、改善了血浆和脂蛋白谱、心脏组织脂质组成的正常化以及与年龄相关的心肌形态变化的显著减少。

结论

所揭示的 N-硬脂酰乙醇胺的作用可能成为开发用于复杂治疗以提高老年人生活质量的新药的基础。

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本文引用的文献

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The Aging Heart: A Molecular and Clinical Challenge.衰老心脏:分子与临床挑战
Int J Mol Sci. 2022 Dec 16;23(24):16033. doi: 10.3390/ijms232416033.
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The role of cytokines/chemokines in an aging skin immune microenvironment.细胞因子/趋化因子在衰老皮肤免疫微环境中的作用。
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Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability.老年人线粒体功能障碍和炎症老化的生物标志物与血压变异性。
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The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine.过氧化物酶体增殖物激活受体γ(PPARγ)参与N-硬脂酰乙醇胺的抗炎活性。
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Aberrant Transferrin and Ferritin Upregulation Elicits Iron Accumulation and Oxidative Inflammaging Causing Ferroptosis and Undermines Estradiol Biosynthesis in Aging Rat Ovaries by Upregulating NF-Κb-Activated Inducible Nitric Oxide Synthase: First Demonstration of an Intricate Mechanism.转铁蛋白和铁蛋白异常上调导致铁积累和氧化炎症老化,通过上调 NF-Κb 激活诱导型一氧化氮合酶破坏雌二醇生物合成在衰老大鼠卵巢中的铁死亡:一种复杂机制的首次证明。
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The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases.内源性大麻素系统在年龄相关性疾病中的治疗潜力
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Anandamide and other N-acylethanolamines: A class of signaling lipids with therapeutic opportunities.花生四烯酸乙醇胺和其他 N-酰基乙醇胺:一类具有治疗潜力的信号脂质。
Prog Lipid Res. 2023 Jan;89:101194. doi: 10.1016/j.plipres.2022.101194. Epub 2022 Sep 20.
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