糖皮质激素对骨骼肌代谢的调控及其机制

Regulation and mechanism of glucocorticoids on skeletal muscle metabolism

糖皮质激素(GCs)对骨骼肌代谢有重要调控作用。GCs可通过促进Pik3r1表达,抑制胰岛素信号转导途径,或通过促进丙酮酸脱氢酶激酶4表达,从而抑制骨骼肌糖摄取及糖原合成,提高血糖水平;GCs可抑制骨骼肌脂质代谢,引起脂质代谢中间体二酰甘油和神经酰胺堆积,诱发骨骼肌胰岛素抵抗; GCs可通过促进Fox O表达,激活泛素-蛋白酶体途径和自噬-溶酶体途径,以及通过激活氧化应激途径,诱导MuRF1与MAFbx表达,或者通过上调C/EBPβ表达,从而促进骨骼肌蛋白质分解; GCs还可通过促进肌肉生长抑制素以及Pik3r1表达,抑制m TOR途径,或者通过上调KLF-15表达,从而抑制骨骼肌蛋白质合成。该文通过综述国内外最新进展,深入探讨GCs对骨骼肌代谢的影响及其分子机制,将为GCs类药物的临床应用提供参考。

Glucocorticoids (GCs) have important regulatory effects on skeletal muscle metabolism.GCs can inhibit skeletal muscle glucose uptake and glycogen synthesis,and improve blood glucose levels by inhibiting Pik3r1 expression,inhibiting insulin signaling pathway,or promoting pyruvate dehydrogenase kinase 4 expression;GCs can inhibit skeletal muscle lipid metabolism,causing the accumulation of lipid metabolism intermediates diacylglycerol and ceramides,and inducing skeletal muscle insulin resistance;GCs can induce MuRF1 and MAFbx expression by promoting FoxO expression,activating the ubiquitin-proteasome system and autophagy lysosome system,and activating oxidative stress system,or promote the protein decomposition of skeletal muscle by up-regulating C/EBPβ expression;GCs can also inhibit the mTOR pathway by promoting myostatin and Pik3r1 expression and inhibit skeletal muscle protein synthesis by up-regulating KLF-15 expression.This article explores the effects of GCs on skeletal muscle metabolism and its molecular mechanisms by tracking the latest developments at home and abroad,which will provide reference for the clinical application of GCs.