肌红蛋白缺乏会损害最大摄氧量和运动能力：来自肌红蛋白缺失小鼠的启示。

Zoladz Jerzy A, Grandys Marcin, Smeda Marta, Kij Agnieszka, Kurpinska Anna, Kwiatkowski Grzegorz, Karasinski Janusz, Hendgen-Cotta Ulrike, Chlopicki Stefan, Majerczak Joanna

Chair of Exercise Physiology and Muscle Bioenergetics, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland.

Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.

J Physiol. 2024 Mar;602(5):855-873. doi: 10.1113/JP285067. Epub 2024 Feb 20.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( ) and exercise performance in myoglobin knockout mice (Mb ) when compared to control mice (Mb ). Furthermore, we also studied NO bioavailability, assessed as nitrite (NO ) and nitrate (NO ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb and in Mb mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb mice had significantly reduced maximal running performance (P < 0.001). expressed in ml min in Mb mice was 37% lower than in Mb mice (P < 0.001) and 13% lower when expressed in ml min kg body mass (P = 0.001). Additionally, Mb mice had significantly lower plasma, heart and locomotory muscle NO levels at rest. During exercise NO increased significantly in the heart and locomotory muscles of Mb and Mb mice, whereas no significant changes in NO were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb ) possess lower maximal oxygen uptake ( ) and poorer maximal running performance than control mice (Mb ). Respiratory exchange ratio values at high running velocities in Mb mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO bioavailability, but does not affect exercise-induced NO changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb mouse model.

肌红蛋白（Mb）在静息和运动时作为氧储备发挥着重要作用，并且有人提出它在缺氧/酸性条件下可调节一氧化氮（NO）的生物利用度。然而，其在运动过程中的最终作用仍是一个有争议的话题。我们旨在研究与对照小鼠（Mb⁺/⁺）相比，肌红蛋白基因敲除小鼠（Mb⁻/⁻）中肌红蛋白缺乏对最大摄氧量（）和运动能力的影响。此外，我们还研究了Mb⁻/⁻和Mb⁺/⁺小鼠在静息和运动至疲惫时心脏、运动肌肉和血浆中以亚硝酸盐（NO₂⁻）和硝酸盐（NO₃⁻）评估的NO生物利用度。小鼠在跑步机上进行最大递增跑步运动，并进行全身气体交换测量。Mb⁻/⁻小鼠的体重、心脏和后肢肌肉质量较低（P < 0.001）。Mb⁻/⁻小鼠的最大跑步能力显著降低（P < 0.001）。以ml·min⁻¹表示时，Mb⁻/⁻小鼠的比Mb⁺/⁺小鼠低37%（P < 0.001），以ml·min⁻¹·kg⁻¹体重表示时低13%（P = 0.001）。此外，Mb⁻/⁻小鼠在静息时血浆、心脏和运动肌肉中的NO₂⁻水平显著较低。运动期间，Mb⁺/⁺和Mb⁻/⁻小鼠心脏和运动肌肉中的NO₂⁻显著增加，而血浆中NO₃⁻未发现显著变化。我们的研究表明，与最近的观点相反，肌红蛋白缺乏显著损害小鼠的和最大跑步能力。要点：肌红蛋白基因敲除小鼠（Mb⁻/⁻）比对照小鼠（Mb⁺/⁺）具有更低的最大摄氧量（）和更差的最大跑步能力。Mb⁻/⁻小鼠在高跑步速度下的呼吸交换率值高于对照小鼠，这表明在相同跑步速度下，Mb⁻/⁻小鼠的底物利用向葡萄糖代谢转变。肌红蛋白的缺乏降低了基础状态下全身和肌肉的NO生物利用度，但不影响运动诱导的血浆、心脏和运动肌肉中NO₂⁻的变化。本研究表明肌红蛋白对和最大跑步能力至关重要，并解释了为什么以前使用Mb⁻/⁻小鼠模型的研究未能证明肌红蛋白的这种作用。