【摘要】 背景：高血压时内皮祖细胞与脑内皮细胞之间的外泌体通讯受损，这可能是导致高血压脑卒中患者预后不良的关键机制。运动康复是防治高血压脑卒中的重要非药物治疗手段，但具体机制未明。目的：探讨高强度间歇训练对自发性高血压大鼠内皮祖细胞外泌体功能的影响并探讨可能机制。方法：24只雄性自发性高血压大鼠随机分为运动组和对照组，运动组进行6周高强度间歇训练，对照组于笼内安静饲养，然后分离培养骨髓内皮祖细胞并获取外泌体，qPCR检测miR-27a表达量。用血管紧张素Ⅱ和低氧刺激处理脑神经瘤细胞(Neuro-2a细胞)后，与内皮祖细胞外泌体、miR-27a抑制剂共孵育，分为空白组(常氧高糖DMEM培养基培养)、损伤组(血管紧张素Ⅱ联合低氧处理)、损伤+对照外泌体组、损伤+运动外泌体组以及损伤+运动外泌体+miR-27a抑制剂组，评估Neuro-2a细胞外泌体摄取率、细胞存活率、活性氧水平以及细胞色素C、NADPH氧化酶4蛋白表达量。结果与结论：(1)Neuro-2a细胞对运动组内皮祖细胞外泌体的摄取率升高；(2)运动上调内皮祖细胞外泌体以及Neuro-2a细胞中miR-27a表达量(P<0.05)；(3)运动诱导的内皮祖细胞外泌体促进Neuro-2a细胞存活(P<0.05)，降低活性氧水平(P<0.05)，下调细胞色素C和NADPH氧化酶4蛋白表达量(P<0.05)，上述作用在给予miR-27a抑制剂后被削弱(P<0.05)。结果表明：高强度间歇训练诱导的自发性高血压大鼠内皮祖细胞外泌体通过miR-27a途径减轻受损神经元氧化应激。更多还原

【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 q PCR. 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 upregulated 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.更多还原