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日常短暂束缚应激会改变大鼠骨骼肌中的信号通路,导致其萎缩和凋亡。

Daily brief restraint stress alters signaling pathways and induces atrophy and apoptosis in rat skeletal muscle.

机构信息

Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa.

出版信息

Stress. 2010 Mar;13(2):132-41. doi: 10.3109/10253890903089834.

DOI:10.3109/10253890903089834
PMID:19929313
Abstract

Skeletal muscle protein loss, known as atrophy, occurs during inactivity, disease, and aging. Atrophy may be the result of increased catabolic factors, e.g. glucocorticoids, or reduced influence of anabolic factors, e.g. insulin. The purpose of this study was to investigate atrophy, signaling mechanisms, and apoptosis in a rat model of restraint stress in 40 adult male Wistar rats. Due to the anxiolytic effects of Sutherlandia frutescens, we also determined if any of the molecular events in gastrocnemius muscle would be affected by daily treatment with S. frutescens. Rats were randomly assigned to four experimental groups: control placebo (CP); control Sutherlandia (CS) treatment; Restraint Placebo (RP) and Restraint Sutherlandia (RS) treatment. Restraint resulted in a significant increase in myostatin which was significantly reduced with Sutherlandia treatment. In addition, MyoD expression was significantly attenuated in RP and this effect was also counteracted by Sutherlandia treatment. Restraint also resulted in a significant attenuation of the PI3-Kinase/Akt signaling pathway and increased apoptosis which was reversed with Sutherlandia treatment. This study demonstrates for the first time that psychological stress elevates markers of muscle atrophy and apoptosis, whilst a herbal remedy, Sutherlandia, inhibits apoptosis, and signaling pathways associated with muscle atrophy.

摘要

骨骼肌蛋白丢失,即萎缩,发生于不活动、疾病和衰老期间。萎缩可能是由于分解代谢因子(如糖皮质激素)增加,或者合成代谢因子(如胰岛素)的影响减少所致。本研究旨在调查束缚应激大鼠模型中的萎缩、信号机制和细胞凋亡。由于南非醉茄具有抗焦虑作用,我们还确定了每日给予南非醉茄是否会影响比目鱼肌中的任何分子事件。大鼠被随机分配到四个实验组:对照安慰剂(CP);对照南非醉茄(CS)处理;束缚安慰剂(RP)和束缚南非醉茄(RS)处理。束缚导致肌肉生长抑制素显著增加,而南非醉茄处理则显著降低了肌肉生长抑制素。此外,RP 组的 MyoD 表达明显减弱,而南非醉茄处理也对抗了这种作用。束缚还导致 PI3-激酶/Akt 信号通路显著衰减和细胞凋亡增加,而南非醉茄处理则逆转了这种作用。本研究首次表明,心理应激会增加肌肉萎缩和细胞凋亡的标志物,而一种草药南非醉茄可以抑制细胞凋亡和与肌肉萎缩相关的信号通路。

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