高强度间歇运动通过调控氧化应激改善原发性高血压患者内皮祖细胞功能

High-intensity intermittent exercise regulates oxidative stress and improves endothelial progenitor cell function in patients with essential hypertension

  • 摘要:
    背景 内皮祖细胞功能异常所致血管内皮损伤是导致高血压及其靶器官损害的始动环节,其中氧化应激扮演着关键角色。高强度间歇运动是多种慢性病防治的有效手段,然而其对内皮祖细胞的作用与机制鲜有关注。
    目的 观察高强度间歇运动对原发性高血压患者内皮祖细胞功能的影响并探讨氧化应激在其间的作用机制。
    方法 60名原发性高血压患者随机分为对照组和运动组,对照组进行常规药物(包括利尿剂、钙离子阻断剂和β受体阻断剂)治疗,运动组在对照组基础上进行8周(3次·周−1)高强度间歇运动。分别于干预前后,利用肱动脉血流介导的血管舒张(FMD)检测血管内皮功能;取静脉血检测循环内皮祖细胞计数;体外培养内皮祖细胞,分别利用改良Boyden小室实验、Matrigel管腔形成实验检测其迁移和成管能力,超氧化物荧光阴离子探针法检测活性氧水平,脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)染色法检测细胞凋亡,免疫印迹法检测还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶2、NADPH氧化酶4、超氧化物歧化酶蛋白表达量。
    结果 本研究中对照组4例(13.3%)、运动组2例(6.7%)脱落;运动组训练计划完成率为94.9%。与干预前比较,干预后运动组血压降低;肱动脉FMD增加;循环内皮祖细胞数量升高,迁移和成管能力增强,活性氧水平和细胞凋亡率降低,NADPH氧化酶2、NADPH氧化酶4蛋白表达下调,超氧化物歧化酶蛋白表达上调,差异均具有统计学意义(P < 0.05)。对照组上述参数与干预前比较均无统计学意义(P > 0.05)。
    结论 高强度间歇运动调控NADPH氧化酶介导的氧化应激改善原发性高血压患者内皮祖细胞功能并恢复血管内皮功能障碍。

     

    Abstract:
    Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells.
    Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress.
    Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week−1) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase.
    Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05).
    Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

     

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