Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery
Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery
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DOI：
10.1038/s41391-023-00774-z
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发表时间：
2023-12-18
影响因子：
4.8
通讯作者：
Phillips，Bethan E.
中科院分区：
文献类型：
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作者：
Blackwell，James E. M.;Gharahdaghi，Nima;Phillips，Bethan E.
泌尿系肿瘤的手术并发症发生率高，幸存者通常会感到疲劳，体能和生活质量下降。高强度间歇训练（HIIT）作为外科手术前训练已被证明可有效改善泌尿系癌症患者的心肺适应性（CRF），但这种有利适应的机制基础尚不明确。因此，我们的目的是评估生理反应的机制HIIT作为外科prehistoric泌尿系统cancer.Methods19例男性患者计划进行重大泌尿外科手术随机完成4周HIIT prehistoric（71.6 ± 0.75岁，BMI：27.7 ± 0.9 kg·m2）或无干预对照组（71.8 ± 1.1岁，BMI：26.9 ± 1.3 kg·m2）。在干预前后，患者均接受了治疗。股外侧肌活检，以量化HIIT对线粒体氧化磷酸化（OXPHOS）能力、累积肌原纤维肌蛋白合成（MPS）以及合成代谢、分解代谢和胰岛素相关信号传导的影响。C-I（r= 0.80，p = 0.003）、C-IV（r= 0.75，p = 0.008）和C-V（r = 0.61，p = 0.046）的变化与CRF的变化显著相关。无论是MPS（1.81 ± 0.12至2.04 ± 0.14%·天-1，p= 0.39）还是合成代谢或分解代谢蛋白质，HIIT均未上调（p> 0.05）。有，但是，增加磷酸化AS 160 Thr 642（p= 0.046）后HIIT.ConclusionsA HIIT手术prehistoric制度，提高了泌尿系癌症患者的CRF，增强了骨骼肌OXPHOS的能力，这种有利的适应提供潜在的机制解释。HIIT不刺激MPS，这与观察到的无肥大同义。需要将以患者为中心的临床终点与机制研究相结合的大型试验，以确定HIIT预防在该队列中的更广泛影响，并为未来的优化提供信息（即，以增加肌肉质量）。
BackgroundSurgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer.MethodsNineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m2). Before and after the intervention period, patients underwentm. vastus lateralisbiopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling.ResultsOXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p= 0.010) and III (p= 0.045); and a significant correlation between changes in C-I (r= 0.80,p= 0.003), C-IV (r= 0.75,p= 0.008) and C-V (r= 0.61,p= 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day−1,p= 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p> 0.05). There was, however, an increase in phosphorylation of AS160Thr642(p= 0.046) post-HIIT.ConclusionsA HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).