Reid M B, Stokić D S, Koch S M, Khawli F A, Leis A A
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
J Clin Invest. 1994 Dec;94(6):2468-74. doi: 10.1172/JCI117615.
N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically.
N-乙酰半胱氨酸（NAC）是一种非特异性抗氧化剂，它能选择性抑制以低强直频率（而非高强直频率）刺激的啮齿动物骨骼肌的急性疲劳，并以剂量依赖方式降低未疲劳肌肉的收缩功能。本实验检验了NAC预处理可抑制人类急性肌肉疲劳这一假设。对健康志愿者进行了两次研究。受试者通过静脉输注接受150mg/kg的NAC或5%葡萄糖水溶液预处理。然后受试者坐在椅子上，将表面电极置于胫骨前肌（一种混合纤维组成的踝关节背屈肌）的运动点上方。刺激肌肉进行电收缩（40 - 55mA，0.2ms脉冲）并测量力量产生情况。通过测量踝关节背屈肌群最大自主收缩（MVC）期间以及胫骨前肌在1、10、20、40、80和120Hz电刺激期间产生的力量来评估未疲劳肌肉的功能（方案1）。使用10Hz（方案1）或40Hz（方案2）的重复强直刺激产生疲劳；随后使用间歇性刺激监测疲劳恢复情况。然后使用相同方案对侧腿进行研究。NAC预处理未改变未疲劳肌肉的功能；胫骨前肌的MVC表现和力量 - 频率关系未改变。在10Hz刺激引起的疲劳收缩期间，NAC使力量输出增加约15%（P < 0.0001），这种效应在重复收缩3分钟后明显（P < 0.0125），并在整个30分钟方案中持续存在。NAC对40Hz刺激诱导的疲劳或疲劳恢复没有影响。N - 乙酰半胱氨酸预处理可改善疲劳运动期间人类肢体肌肉的表现，表明氧化应激在疲劳过程中起因果作用，并确定抗氧化治疗为一种可能在临床上有用的新型干预措施。
