a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.
b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
Appl Physiol Nutr Metab. 2017 Feb;42(2):117-127. doi: 10.1139/apnm-2016-0363. Epub 2016 Oct 3.
The purpose of this study was to examine the possible mechanism underlying the protective effect of tetramethylpyrazine (TMP) against disuse-induced muscle atrophy. Sprague-Dawley rats were randomly assigned to receive 14 days of hindlimb unloading (HLU, a model of disuse atrophy) or cage controls. The rats were given TMP (60 mg/kg body mass) or vehicle (water) by gavage. Compared with vehicle treatment, TMP significantly attenuated the loss of gastrocnemius muscle mass (-33.56%, P < 0.01), the decrease of cross-sectional area of slow fiber (-10.99%, P < 0.05) and fast fiber (-15.78%, P < 0.01) during HLU. Although TMP failed to further improve recovery of muscle function or fatigability compared with vehicle treatment, it can suppress the higher level of lactate (-22.71%, P < 0.01) induced by HLU. Besides, TMP could effectually reduce the increased protein expression of muscle RING-finger protein 1 induced by HLU (-14.52%, P < 0.01). Furthermore, TMP can ameliorate the calcium overload (-54.39%, P < 0.05), the increase of malondialdehyde content (-19.82%, P < 0.05), the decrease of superoxide dismutase activity (21.34%, P < 0.05), and myonuclear apoptosis (-78.22%, P < 0.01) induced by HLU. Moreover, TMP significantly reduced HLU-induced increase of Bax to B-cell lymphoma 2 (-36.36%, P < 0.01) and cytochrome c release (-36.16%, P < 0.05). In conclusion, TMP attenuated HLU-induced gastrocnemius muscle atrophy through suppression of Ca/reactive oxygen species increase and consequent proteolysis and apoptosis. Therefore, TMP might exhibit therapeutic effect against oxidative stress, cytosolic calcium overload, and mitochondrial damage in disuse-induced muscle atrophy.
本研究旨在探讨川芎嗪（TMP）防治废用性肌萎缩的可能作用机制。将 Sprague-Dawley 大鼠随机分为接受 14 天后肢去负荷（HLU，废用性萎缩模型）或笼对照。通过灌胃给予大鼠 TMP（60mg/kg 体重）或载体（水）。与载体处理相比，TMP 显著减轻了腓肠肌质量的损失（-33.56%，P <0.01）、慢纤维（-10.99%，P <0.05）和快纤维（-15.78%，P <0.01）横截面积的减少。尽管 TMP 未能进一步改善与载体处理相比肌肉功能或疲劳性的恢复，但它可以抑制 HLU 引起的乳酸水平升高（-22.71%，P <0.01）。此外，TMP 可以有效降低 HLU 引起的肌肉环指蛋白 1 表达增加（-14.52%，P <0.01）。此外，TMP 可以改善 HLU 引起的钙超载（-54.39%，P <0.05）、丙二醛含量增加（-19.82%，P <0.05）、超氧化物歧化酶活性降低（21.34%，P <0.05）和核凋亡减少（-78.22%，P <0.01）。此外，TMP 显著降低了 HLU 诱导的 Bax 对 B 细胞淋巴瘤 2 的增加（-36.36%，P <0.01）和细胞色素 c 释放（-36.16%，P <0.05）。综上所述，TMP 通过抑制 Ca/活性氧增加以及随后的蛋白水解和凋亡来减轻 HLU 引起的腓肠肌萎缩。因此，TMP 可能对废用性肌萎缩中的氧化应激、胞质钙超载和线粒体损伤具有治疗作用。
