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内皮祖细胞移植可修复全脑照射后小鼠的血管损伤。

Endothelial progenitor cell transplantation restores vascular injury in mice after whole-brain irradiation.

机构信息

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, China.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, China.

出版信息

Brain Res. 2020 Nov 1;1746:147005. doi: 10.1016/j.brainres.2020.147005. Epub 2020 Jul 2.

Abstract

Vascular damage plays an important role in the pathogenesis of radiation-induced brain injury (RBI). Endothelial progenitor cells (EPCs) are responsible for maintaining and repairing endothelial function, and have become a promising method for the treatment of cerebrovascular diseases. However, whether EPC transplantation plays a protective role in RBI has not been fully elucidated. Therefore, the present study investigated the effects of bone marrow-derived EPC transplantation in a whole-brain irradiation (WBI) mouse model. Mice were divided into the three groups: control group, irradiation group and EPCs group. Phosphate buffered saline or EPCs were intravenously injected into mice one week after irradiation, and brains were analyzed eight weeks after injection. Flow cytometry demonstrated that irradiation led to a significant reduction in the peripheral blood EPC count; however, EPC transplantation led to a significant increase in the circulating EPCs. Intravital two-photon imaging and western blotting demonstrated that EPC transplantation reversed the effects of irradiation by decreasing blood-brain barrier permeability and increasing the expression of tight junction proteins in the brain. Additionally, immunofluorescence staining revealed that the brain microvascular density was higher in the EPCs group than the irradiation group. Therefore, EPC transplantation may restore damage caused by WBI to the blood-brain barrier, tight junctions, and cerebral capillary density. These results highlight the potential beneficial effects of EPC transplantation on vascular damage induced by RBI.

摘要

血管损伤在放射性脑损伤(RBI)的发病机制中起着重要作用。内皮祖细胞(EPCs)负责维持和修复内皮功能,已成为治疗脑血管疾病的一种有前途的方法。然而,EPC 移植是否对 RBI 具有保护作用尚未得到充分阐明。因此,本研究探讨了骨髓源性 EPC 移植在全脑照射(WBI)小鼠模型中的作用。将小鼠分为三组:对照组、照射组和 EPC 组。照射后一周,通过静脉注射磷酸盐缓冲液或 EPC 至小鼠体内,注射 8 周后分析大脑。流式细胞术表明,照射导致外周血 EPC 计数显著减少;然而,EPC 移植导致循环 EPCs 显著增加。活体双光子成像和 Western blot 表明,EPC 移植通过降低血脑屏障通透性和增加脑内紧密连接蛋白的表达来逆转照射的影响。此外,免疫荧光染色显示 EPC 组的脑微血管密度高于照射组。因此,EPC 移植可能恢复 WBI 对血脑屏障、紧密连接和脑毛细血管密度的损伤。这些结果强调了 EPC 移植对 RBI 引起的血管损伤的潜在有益作用。

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