Wallis Tim J M, Minnion Magdalena, Freeman Anna, Bates Andrew, Otto James M, Wootton Stephen A, Fletcher Sophie V, Grocott Michael P W, Feelisch Martin, Jones Mark G, Jack Sandy
NIHR Southampton Biomedical Research Centre, Respiratory and Critical Care, University Hospital Southampton, Southampton SO16 6YD, UK.
Academic School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
Antioxidants (Basel). 2023 Aug 20;12(8):1645. doi: 10.3390/antiox12081645.
Exercise training is recommended for patients with idiopathic pulmonary fibrosis (IPF); however, the mechanism(s) underlying its physiological benefits remain unclear. We investigated the effects of an individualised aerobic interval training programme on exercise capacity and redox status in IPF patients. IPF patients were recruited prospectively to an 8-week, twice-weekly cardiopulmonary exercise test (CPET)-derived structured responsive exercise training programme (SRETP). Systemic redox status was assessed pre- and post-CPET at baseline and following SRETP completion. An age- and sex-matched non-IPF control cohort was recruited for baseline comparison only. At baseline, IPF patients ( = 15) had evidence of increased oxidative stress compared with the controls as judged by; the plasma reduced/oxidised glutathione ratio (median, control 1856 vs. IPF 736 = 0.046). Eleven IPF patients completed the SRETP (median adherence 88%). Following SRETP completion, there was a significant improvement in exercise capacity assessed via the constant work-rate endurance time (+82%, = 0.003). This was accompanied by an improvement in post-exercise redox status (in favour of antioxidants) assessed via serum total free thiols (median increase, +0.26 μmol/g protein = 0.005) and total glutathione concentration (+0.73 μM = 0.03), as well as a decrease in post-exercise lipid peroxidation products (-1.20 μM = 0.02). Following SRETP completion, post-exercise circulating nitrite concentrations were significantly lower compared with baseline (-0.39 μM = 0.04), suggestive of exercise-induced nitrite utilisation. The SRETP increased both endurance time and systemic antioxidant capacity in IPF patients. The observed reduction in nitrite concentrations provides a mechanistic rationale to investigate nitrite/nitrate supplementation in IPF patients.
推荐特发性肺纤维化（IPF）患者进行运动训练；然而，其生理益处背后的机制仍不清楚。我们研究了个体化有氧间歇训练方案对IPF患者运动能力和氧化还原状态的影响。前瞻性招募IPF患者参加为期8周、每周两次的心肺运动试验（CPET）衍生的结构化响应运动训练方案（SRETP）。在基线和SRETP完成后，于CPET前后评估全身氧化还原状态。仅招募年龄和性别匹配的非IPF对照队列进行基线比较。在基线时，与对照组相比，IPF患者（n = 15）有氧化应激增加的证据，通过血浆还原型/氧化型谷胱甘肽比率判断（中位数，对照组1856 vs. IPF 736，P = 0.046）。11名IPF患者完成了SRETP（中位数依从性88%）。SRETP完成后，通过恒定工作率耐力时间评估的运动能力有显著改善（增加82%，P = 0.003）。这伴随着通过血清总游离巯基（中位数增加，+0.26 μmol/g蛋白质，P = 0.005）和总谷胱甘肽浓度（+0.73 μM，P = 0.03）评估的运动后氧化还原状态的改善（有利于抗氧化剂），以及运动后脂质过氧化产物的减少（-1.20 μM，P = 0.02）。SRETP完成后，运动后循环亚硝酸盐浓度与基线相比显著降低（-0.39 μM，P = 0.04），提示运动诱导的亚硝酸盐利用。SRETP增加了IPF患者的耐力时间和全身抗氧化能力。观察到的亚硝酸盐浓度降低为研究IPF患者补充亚硝酸盐/硝酸盐提供了机制依据。
