纳米硒标记灵菌红素对慢性不可预知温和应激大鼠的神经保护作用与其抗氧化、抗炎、抗凋亡和神经调节活性有关。

Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities.

机构信息

Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.

出版信息

Int J Nanomedicine. 2021 Dec 30;16:8447-8464. doi: 10.2147/IJN.S323436. eCollection 2021.

DOI:10.2147/IJN.S323436

PMID:35002238

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8722537/

Abstract

PURPOSE

Depression is a mood disorder accompanied by intensive molecular and neurochemical alterations. Currently, available antidepressant therapies are not fully effective and are often accompanied by several adverse impacts. Accordingly, the ultimate goal of this investigation was to clarify the possible antidepressant effects of prodigiosins (PDGs) loaded with selenium nanoparticles (PDGs-SeNPs) in chronic unpredictable mild stress (CUMS)-induced depression-like behavior in rats.

METHODS

Sixty Sprague Dawley rats were randomly allocated into six groups: control, CUMS group (depression model), fluoxetine (Flu, 10 mg/kg)+CUMS, PDGs+CUMS (300 mg/kg), sodium selenite (NaSeO, 400 mg/kg)+CUMS, and PDGs-SeNPs+CUMS (200 mg/kg). All treatments were applied orally for 28 consecutive days.

RESULTS

PDGs-SeNPs administration prevented oxidative insults in hippocampal tissue, as demonstrated by decreased oxidant levels (nitric oxide and malondialdehyde) and elevated innate antioxidants (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase), in addition to the upregulated expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in rats exposed to CUMS. Additionally, PDGs-SeNPs administration suppressed neuroinflammation in hippocampal tissue, as determined by the decreased production of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and interleukin-6), increased anti-inflammatory cytokine interleukin-10, and decreased inflammatory mediators (prostaglandin E2, cyclooxygenase-2, and nuclear factor kappa B). Moreover, PDGs-SeNPs administration in stressed rats inhibited neuronal loss and the development of hippocampal apoptosis through enhanced levels of B cell lymphoma 2 and decreased levels of caspase 3 and Bcl-2-associated X protein. Interestingly, PDGs-SeNPs administration improved hormonal levels typically disrupted by CUMS exposure and significantly modulated hippocampal levels of monoamines, brain-derived neurotrophic factor, monoamine oxidase, and acetylcholinesterase activities, in addition to upregulating the immunoreactivity of glial fibrillary acidic protein in CUMS model rats.

CONCLUSION

PDGs-SeNPs may serve as a prospective antidepressant candidate due to their potent antioxidant, anti-inflammatory, and neuroprotective potential.

摘要

目的

抑郁症是一种伴有强烈分子和神经化学改变的情绪障碍。目前，可用的抗抑郁疗法并不完全有效，并且常常伴有多种不良反应。因此，本研究的最终目的是阐明载硒纳米粒子的灵菌红素（PDGs-SeNPs）对慢性不可预测轻度应激（CUMS）诱导的大鼠抑郁样行为可能具有的抗抑郁作用。

方法

将 60 只 Sprague Dawley 大鼠随机分为 6 组：对照组、CUMS 组（抑郁模型）、氟西汀（Flu，10mg/kg）+CUMS、PDGs+CUMS（300mg/kg）、亚硒酸钠（NaSeO，400mg/kg）+CUMS 和 PDGs-SeNPs+CUMS（200mg/kg）。所有治疗均连续口服 28 天。

结果

PDGs-SeNPs 给药可防止 CUMS 大鼠海马组织的氧化损伤，表现为氧化应激水平（一氧化氮和丙二醛）降低，内源性抗氧化剂（谷胱甘肽、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、超氧化物歧化酶和过氧化氢酶）升高，核因子红细胞 2 相关因子 2 和血红素加氧酶-1 的表达上调。此外，PDGs-SeNPs 给药可抑制海马组织神经炎症，表现为促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β 和白细胞介素-6）生成减少，抗炎细胞因子白细胞介素-10 增加，炎症介质（前列腺素 E2、环氧化酶-2 和核因子 kappa B）减少。此外，PDGs-SeNPs 给药可通过增加 B 细胞淋巴瘤 2 水平和降低 caspase 3 和 Bcl-2 相关 X 蛋白水平来抑制应激大鼠的神经元丢失和海马细胞凋亡的发展。有趣的是，PDGs-SeNPs 给药可改善 CUMS 暴露引起的激素水平异常，并显著调节 CUMS 模型大鼠海马中单胺、脑源性神经营养因子、单胺氧化酶和乙酰胆碱酯酶的活性，同时上调胶质纤维酸性蛋白的免疫反应性。