Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Biomolecules. 2020 Mar 12;10(3):441. doi: 10.3390/biom10030441.
Alcohol use and aging are risk factors for falls requiring immobilization and leading to skeletal muscle atrophy. Skeletal muscle regeneration is integral to post-immobilization recovery. This study aimed to elucidate the effects of alcohol and ovarian hormone loss on the expression of genes implicated in muscle regeneration. Three-month-old female rats received an ovariectomy or a sham surgery, consumed an alcohol-containing or control diet for 10 weeks, were subjected to unilateral hind limb immobilization for seven days, and finally were allowed a three (3d)- or 14 (14d)-day recovery. Immobilization decreased the quadriceps weight at 3d and 14d, and alcohol decreased the quadriceps weight at 14d in the nonimmobilized hind limb (NI). At 3d, alcohol decreased gene expression of myoblast determination protein (MyoD) in the immobilized hind limb (IMM) and myocyte enhancer factor (Mef)2C and tumor necrosis factor (TNF)α in NI, and ovariectomy increased MyoD and decreased TNFα expression in NI. At 14d, alcohol increased the gene expression of Mef2C, MyoD, TNFα, and transforming growth factor (TFG)β in IMM and decreased monocyte chemoattractant protein (MCP)1 expression in NI; ovariectomy increased TNFα expression in NI, and alcohol and ovariectomy together increased Mef2C expression in NI. Despite increased TGFβ expression, there was no concomitant alcohol-mediated increase in collagen in IMM at 14d. Overall, these data indicate that alcohol dysregulated the post-immobilization alteration in the expression of genes implicated in regeneration. Whether alcohol-mediated molecular changes correspond with post-immobilization functional alterations remains to be determined.
酒精使用和衰老都是导致需要固定并导致骨骼肌萎缩的跌倒的风险因素。骨骼肌再生是固定后恢复的重要组成部分。本研究旨在阐明酒精和卵巢激素丧失对肌肉再生相关基因表达的影响。三个月大的雌性大鼠接受卵巢切除术或假手术，饮用含酒精或对照饮食 10 周，单侧后肢固定 7 天，最后允许 3（3d）或 14（14d）天恢复。固定在 3d 和 14d 时降低了四头肌重量，而酒精在非固定后肢（NI）的 14d 时降低了四头肌重量。在 3d 时，酒精降低了固定后肢（IMM）中成肌细胞决定蛋白（MyoD）和肌细胞增强因子（Mef）2C 的基因表达，以及 NI 中的肿瘤坏死因子（TNF）α，而卵巢切除术增加了 NI 中的 MyoD 和减少了 TNFα 的表达。在 14d 时，酒精增加了 IMM 中 Mef2C、MyoD、TNFα 和转化生长因子（TGF）β的基因表达，降低了 NI 中单核细胞趋化蛋白（MCP）1 的表达；卵巢切除术增加了 NI 中的 TNFα 表达，酒精和卵巢切除术共同增加了 NI 中的 Mef2C 表达。尽管 TGFβ 的表达增加，但在 14d 时，IMM 中没有伴随酒精介导的胶原增加。总的来说，这些数据表明，酒精失调了固定后再生相关基因表达的改变。酒精介导的分子变化是否与固定后的功能改变相对应仍有待确定。
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