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通过靶向Bax/Bcl2通路并使用负载地塞米松的富血小板血浆外泌体调节TNF-α/IL-10来改善脊髓损伤症状。

Improvement of spinal cord injury symptoms by targeting the Bax/Bcl2 pathway and modulating TNF-α/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasone.

作者信息

Akbari-Gharalari Naeimeh, Ghahremani-Nasab Maryam, Naderi Roya, Aliyari-Serej Zeinab, Karimipour Mohammad, Shahabi Parviz, Ebrahimi-Kalan Abbas

机构信息

Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Tissue Engineering, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

AIMS Neurosci. 2023 Nov 20;10(4):332-353. doi: 10.3934/Neuroscience.2023026. eCollection 2023.

DOI:10.3934/Neuroscience.2023026
PMID:38188010
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10767060/
Abstract

Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.

摘要

脊髓损伤(SCI)是一种使人衰弱的病症,由于脊髓的自我再生能力有限,导致感觉和运动功能受损。为了解决这个问题,联合治疗已被提议作为SCI再生的一种有效治疗策略。在本研究中,将负载地塞米松的富血小板血浆(PRP)衍生的外泌体用于SCI压迫小鼠模型。使用超速离心和超声处理方法制备负载地塞米松(Dex)的PRP衍生的外泌体,并通过静脉注射将其给予小鼠。在为期四周的时间后,进行行为评估以评估功能恢复情况,并对包括与细胞凋亡和抗细胞凋亡相关的基因表达、血清细胞因子浓度和组织采样在内的各种指标进行了全面检查。本研究结果表明,与模型组相比,用负载Dex的PRP衍生的外泌体(ExoDex)处理的小鼠表现出TNF-α和IL-10水平的改变,同时Bax表达降低,Bcl2表达增加。此外,静脉注射ExoDex减小了损伤部位的大小、淋巴细胞浸润、空泡化、空洞大小和组织紊乱,同时还改善了运动恢复。我们认为,负载外泌体的Dex疗法作为一种有前景且与临床相关的脊髓损伤修复方法具有潜力。然而,在该领域需要进一步广泛研究以验证和证实本研究中呈现的结果。

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