High-intensity interval training improves the function of exosomes derived from endothelial progenitor cells in spontaneously hypertensive rats

doi:10.12307/2026.713

Abstract

Abstract: BACKGROUND: Under hypertensive conditions, exosome communication between endothelial progenitor cells and brain endothelial cells is impaired, which may be a key mechanism leading to poor prognosis in patients with hypertensive stroke. Exercise rehabilitation is an important non-drug means of preventing and treating hypertensive stroke, but the specific mechanism is unclear.
OBJECTIVE: To investigate the effect of high-intensity interval training on the function of exosomes from endothelial progenitor cells in spontaneously hypertensive rats and explore the possible mechanism.
METHODS: Twenty-four male spontaneously hypertensive rats were randomly assigned into exercise group or control group. The animals in the exercise group underwent 6 weeks of high-intensity interval training, while those in the control group were kept quietly in cage. After the experiment, bone marrow endothelial progenitor cells were isolated and cultured, and exosomes were obtained to detect the expression of miR-27a using qPCR. After treating neuroblastoma N2a (Neuro-2a) with angiotensin II and hypoxia, they were co-incubated with endothelial progenitor cell-derived exosomes and a miR-27a inhibitor. The cells were then divided into the following groups: a blank group (cultured in normoxic high-glucose DMEM medium), an injury group (treated with angiotensin II combined with hypoxia), an injury + control exosome group, an injury + exercise exosome group, and an injury + exercise exosome + miR-27a inhibitor group. The following parameters were assessed: exosome uptake rate, cell viability, reactive oxygen species levels, and the expression levels of cytochrome C and NADPH oxidase 4 protein.
RESULTS AND CONCLUSION: (1) Exercise could increase the uptake efficiency of endothelial progenitor cell exosomes by Neuro-2a cells. (2) Exercise up-regulated the expression of miR-27a in endothelial progenitor cell exosomes and Neuro-2a cells (P < 0.05). (3) Exercise-induced endothelial progenitor cell exosomes improved the survival of Neuro-2a cells (P < 0.05), reduced the level of reactive oxygen species (P < 0.05) and down-regulated the protein expression of cytochrome C and NADPH oxidase 4 (P < 0.05), while the above effects were weakened after administration of miR-27a inhibitor (P < 0.05). To conclude, high-intensity interval training-induced exosomes from endothelial progenitor cells in spontaneously hypertensive rats alleviate the oxidative stress of damaged neurons through the miR-27a pathway.

Key words: high-intensity interval training, spontaneously hypertensive rats, endothelial progenitor cell, exosome, stroke, Neuro-2a cells

CLC Number:

Lu Anran, Wang Chenyu, Zhang Yan, Huang Huasheng. High-intensity interval training improves the function of exosomes derived from endothelial progenitor cells in spontaneously hypertensive rats[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(18): 4627-4637.

Figures/Tables 8

2.5.4 Neuro-2a细胞与内皮祖细胞外泌体共培养对Neuro-2a细胞存活率的影响与空白组比较，血管紧张素Ⅱ联合缺氧处理后Neuro-2a细胞存活率下降(P < 0.05)；与血管紧张素Ⅱ联合缺氧处理比较，添加对照组和运动组内皮祖细胞外泌体后Neuro-2a 细胞存活率均升高(P < 0.05)；与添加对照组内皮祖细胞外泌体比较，添加运动组内皮祖细胞外泌体后Neuro-2a细胞存活率升高(P < 0.05)；与添加运动组内皮祖细胞外泌体比较，使用miR-27a抑制剂后Neuro-2a细胞存活率降低(P < 0.05)，见图8。 2.5.5 Neuro-2a细胞与内皮祖细胞外泌体共培养对Neuro-2a细胞活性氧水平的影响免疫荧光观察显示，活性氧呈现绿色荧光。见图9A。与空白组比较，血管紧张素Ⅱ联合缺氧处理后Neuro-2a细胞活性氧水平升高(P < 0.05)；与血管紧张素Ⅱ联合缺氧处理比较，添加对照组和运动组内皮祖细胞外泌体后Neuro-2a细胞活性氧水平均下降(P < 0.05)；与添加对照组内皮祖细胞外泌体比较，添加运动组内皮祖细胞外泌体后Neuro-2a细胞活性氧水平降低(P < 0.05)；与添加运动组内皮祖细胞外泌体比较，使用miR-27a抑制剂后Neuro-2a细胞活性氧水平升高(P < 0.05)，见图9B。 2.5.6 Neuro-2a细胞与内皮祖细胞外泌体共培养对Neuro-2a细胞相关蛋白表达的影响与空白组比较，血管紧张素Ⅱ联合缺氧处理后Neuro-2a细胞中细胞色素C和NADPH氧化酶4蛋白表达上调(P < 0.05)；与血管紧张素Ⅱ联合缺氧处理比较，添加对照组和运动组内皮祖细胞外泌体后Neuro-2a细胞中细胞色素C和NADPH氧化酶4蛋白表达均下调(P < 0.05)；与添加对照组内皮祖细胞外泌体比较，添加运动组内皮祖细胞外泌体后Neuro-2a细胞中细胞色素C和NADPH氧化酶4蛋白表达降低(P < 0.05)；与添加运动组内皮祖细胞外泌体比较，使用miR-27a抑制剂后Neuro-2a细胞中细胞色素C和NADPH氧化酶4蛋白表达升高(P < 0.05)，见图10。"

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