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来源于脂肪源干细胞的载辅酶 Q10 外泌体对阿尔茨海默病大鼠模型的神经保护作用。

Neuroprotective effects of coenzyme Q10-loaded exosomes obtained from adipose-derived stem cells in a rat model of Alzheimer's disease.

机构信息

Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Biomed Pharmacother. 2022 Aug;152:113224. doi: 10.1016/j.biopha.2022.113224. Epub 2022 Jun 6.

DOI:10.1016/j.biopha.2022.113224
PMID:35679720
Abstract

Alzheimer's disease (AD) is a degenerative disease that causes memory and learning impairments as well as dementia. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with AD. This study investigated the effects of drug delivery of COQ10 by exosomes derived from adipose-derived stem cells (ADSCs-Exo) on cognition, memory, and neuronal proliferation in a rat model of Streptozotocin (STZ)-induced AD. Since the establishment of the AD model, the rats have received intraperitoneal injections of CoQ10, Exo, or CoQ10-loaded ADSCs-Exo (Exo+ CoQ10). The passive avoidance test and the Morris water maze (MWM) were used to assess memory and cognition changes. Cell density was determined using histological methods. The expression of BDNF was measured using an ELISA kit. SOX2 expression was determined using immunohistochemistry. According to the results of the MWM and passive avoidance task, Exo+CoQ10 significantly improved STZ-induced memory impairment compared to CoQ10 and Exo groups alone. Furthermore, BDNF expression increased in the STZ-induced rats after Exo+ CoQ10, when compared to the CoQ10 and Exo groups. In addition, Exo+CoQ10 had the highest cell density and SOX2 gene expression, when compared to the CoQ10 and Exo groups. According to the findings of this study, Exo+ COQ10 enhanced cognition and memory deficiency in Alzheimer's disease by boosting BDNF and SOX2 levels in the hippocampus. Hence, the use of exosomes derived from adipose-derived stem cells as the carrier of CoQ10 may increase the therapeutic effect of CoQ10, which can possibly be due to the regenerative properties of the exosomes.

摘要

阿尔茨海默病(AD)是一种退行性疾病,会导致记忆和学习障碍以及痴呆。辅酶 Q10(CoQ10)是一种抗炎和抗氧化应激补充剂,可以改善与 AD 相关的炎症和氧化应激。本研究探讨了脂肪来源干细胞(ADSCs-Exo)衍生的外泌体输送 CoQ10 对链脲佐菌素(STZ)诱导 AD 大鼠模型认知、记忆和神经元增殖的影响。自 AD 模型建立以来,大鼠接受了 CoQ10、Exo 或负载 CoQ10 的 ADSC-Exo(Exo+CoQ10)的腹腔注射。使用被动回避试验和 Morris 水迷宫(MWM)评估记忆和认知变化。使用组织学方法测定细胞密度。使用 ELISA 试剂盒测定 BDNF 的表达。使用免疫组织化学测定 SOX2 表达。根据 MWM 和被动回避任务的结果,与 CoQ10 和 Exo 组相比,Exo+CoQ10 显著改善了 STZ 诱导的记忆障碍。此外,与 CoQ10 和 Exo 组相比,Exo+CoQ10 后 STZ 诱导的大鼠 BDNF 表达增加。此外,与 CoQ10 和 Exo 组相比,Exo+CoQ10 具有最高的细胞密度和 SOX2 基因表达。根据本研究的结果,Exo+COQ10 通过提高海马体中的 BDNF 和 SOX2 水平,增强了阿尔茨海默病的认知和记忆缺陷。因此,使用脂肪来源干细胞衍生的外泌体作为 CoQ10 的载体可能会增加 CoQ10 的治疗效果,这可能是由于外泌体的再生特性。

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