骨骼肌是人類及動(dòng)物機(jī)體中分布最廣的組織，在維持機(jī)體的正常運(yùn)動(dòng)機(jī)能與能量代謝穩(wěn)態(tài)中起重要作用。此外，對(duì)農(nóng)業(yè)動(dòng)物而言，骨骼肌是供人類食用的最主要部位，其生長速度也是農(nóng)業(yè)動(dòng)物生產(chǎn)中重要的經(jīng)濟(jì)性狀。骨骼肌的生理狀態(tài)與機(jī)體營養(yǎng)狀態(tài)息息相關(guān)，在硒營養(yǎng)領(lǐng)域，以往的研究更多集中在缺硒引起的骨骼肌疾病方面，而對(duì)硒狀態(tài)與骨骼肌的胚后生長之間關(guān)系的研究卻鮮有報(bào)道。

 

　　該研究以斑馬魚為模型系統(tǒng)性地研究了不同硒狀態(tài)（缺硒、足量硒及高硒）對(duì)骨骼肌胚后生長的影響，并對(duì)其內(nèi)在機(jī)理進(jìn)行了初步探討。通過分析全魚硒轉(zhuǎn)錄組、氧化狀態(tài)及生長性能，確定了斑馬魚的最低硒（酵母硒）需求量為0.34 mg/kg，而≤0.22 mg/kg或≥0.57 mg/kg將分別導(dǎo)致斑馬魚處于缺硒及高硒狀態(tài)。

 

　　通過對(duì)骨骼肌組織形態(tài)學(xué)進(jìn)行分析發(fā)現(xiàn)，相比于足量硒，缺硒及高硒導(dǎo)致骨骼肌橫截面積減少、肌纖維平均直徑減少、細(xì)肌纖維增多及粗肌纖維減少，表明缺硒及高硒影響了骨骼肌的肥大性生長；進(jìn)一步對(duì)骨骼肌纖維肥大相關(guān)生物學(xué)事件進(jìn)行分析，發(fā)現(xiàn)硒狀態(tài)的改變影響了骨骼肌纖維中蛋白質(zhì)周轉(zhuǎn)代謝，但缺硒與高硒的影響形式存在著差異：相比于足量硒，缺硒抑制了Akt-TORC1通路活性并激活了eIF2α從而抑制了蛋白質(zhì)合成，并促進(jìn)了自噬-溶酶體途徑及泛素-蛋白酶體途徑的激活從而加快了蛋白質(zhì)降解，而高硒對(duì)蛋白質(zhì)合成并無影響但高度激活了泛素-蛋白酶體途徑從而導(dǎo)致蛋白質(zhì)的快速降解。

 

　　【英文摘要】

 

　　Background: Selenium （Se） status is closely related to skeletal muscle physiological status. However, its influence on skeletal muscle growth has not been well studied.

 

　　Objectives: This study aimed to analyze the impacts of overall Se status （deficient, adequate, and high） on skeletal muscle growth using a growing zebrafish model.

 

　　Methods: Zebrafish （1.5-mo-old） were fed graded levels of Se （deficient: 0.10 mg Se/kg; marginally deficient: 0.22 mg Se/kg; adequate: 0.34 mg Se/kg; high: 0.44, 0.57, and 0.69 mg Se/kg） as Se-enriched yeast for 30 d. Zebrafish growth, and Se accumulation, selenoenzyme activity, selenotranscriptome profiles, and oxidative status in the whole body, and selenotranscriptome profiles, histological characteristics, biochemicals, and gene and protein expression profiles related to muscle growth in the skeletal muscle were analyzed by model fitting and/or 1-factor ANOVA.

 

　　Results: Se status biomarkers within the whole body and skeletal muscle indicated that 0.34 mg Se/kg was adequate for growing zebrafish. For biomarkers related to skeletal muscle growth, compared with 0.34 mg Se/kg, 0.10 mg Se/kg decreased the white muscle cross-sectional area （WMCSA） and the mean diameter of white muscle fibers （MDWMF） by 14.4%–15.1%, inhibited protein kinase B–target of rapamycin complex 1 signaling by 63.7%–68.5%, and stimulated the autophagy–lysosome pathway by 1.07 times and the ubiquitin–proteasome pathway （UPP） by 96.0% （P < 0.05）， whereas 0.22 mg Se/kg only decreased the WMCSA by 7.8% （P < 0.05）； furthermore, 0.44 mg Se/kg had no clear effects on skeletal muscle biomarkers, whereas 0.57–0.69 mg Se/kg decreased the WMCSA and MDWMF by 6.3%–25.9% and 5.1%–21.3%, respectively, and stimulated the UPP by 2.23 times （P < 0.05）。

 

　　Conclusions: A level of 0.34 mg Se/kg is adequate for the growth of zebrafish skeletal muscle, whereas ≤0.10 and ≥0.57 mg Se/kg are too low or too high, respectively, for maintaining efficient protein accretion and normal hypertrophic growth.

 

　　論文鏈接：

 

　　Selenium Status Affects Hypertrophic Growth of Skeletal Muscle in Growing Zebrafish by Mediating Protein Turnover | The Journal of Nutrition | Oxford Academic （oup.com）