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腺苷酸激活蛋白激酶磷酸化障碍导致烧伤后骨骼肌脂质沉积的实验研究

, PP. 845-850

Keywords: 烧伤,骨骼肌脂质沉积,腺苷酸激活蛋白激酶,乙酰辅酶a羧化酶,肉碱脂酰转移酶-

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Abstract:

目的探讨影响腺苷酸激活蛋白激酶(AMPactivatedproteinkinase,AMPK)/乙酰辅酶a羧化酶(acetylCoAcarboxylase,ACC)信号通路导致烧伤后骨骼肌脂质沉积(intramyocellularlipids,IMCLs)的分子机制。方法采用30%体表面积Ⅲ度烧伤小鼠模型,将54只BALB/c小鼠按随机数字表法分为正常对照组、AMPK激活剂(acadesine,AICAR)组、烧伤组、烧伤+AICAR组,同位素标记法检测各组小鼠腓肠肌中肉碱脂酰转移酶-1(carnitinepalmitoyltransferase-1,CPT1)活性变化,Westernblot检测各组小鼠腓肠肌中AMPK-α、p-AMPK-α、ACC及p-ACC表达水平,通过油红O染色和甘油三酯(triglyceride,TG)测定法评估各组小鼠腓肠肌IMCLs情况。结果烧伤后小鼠腓肠肌中ACC表达量较伤前显著升高(P<0.05),而AMPK-α、p-AMPK-α、p-ACC以及CPT1活性均显著降低(P<0.05)。在AICAR作用下,正常小鼠腓肠肌中p-AMPK-α表达显著升高[(1.16±0.08)vs(2.38±0.22),P<0.05],p-ACC表达显著升高[(1.74±0.10)vs(3.72±0.18),P<0.05],CPT1活性显著升高[(2.95±0.39)nmol/(min·mg)vs?(6.35±0.68)nmol/(min·mg),P<0.05],TG含量显著降低[(3.88±0.40)mmol/gvs(2.89±0.54)mmol/g,P<0.05]。烧伤+AICAR组小鼠腓肠肌中p-AMPK-α、p-ACC、CPT1活性及甘油三酯含量较烧伤组无显著差异(P>0.05)。正常对照组和AICAR组正常小鼠腓肠肌组织切片油红O染色未见明显脂质沉积,而烧伤组和烧伤+AICAR组烧伤小鼠腓肠肌组织切片油红O染色均显示有大量脂质沉积,两组间并无显著差异(P>0.05)。结论骨骼肌中AMPK磷酸化障碍是烧伤后IMCLs的重要分子机制之一。

References

[1]  Cohen S, Nathan J A, Goldberg A L. Muscle wasting in disease: molecular mechanisms and promising therapies[J]. Nat Rev Drug Discov, 2015, 14(1): 58-74. [2]Porter C, Herndon D N, Sidossis L S, et al. The impact of severe burns on skeletal muscle mitochondrial function[J]. Burns, 2013, 39(6): 1039-1047. [3]Williams F N, Branski L K, Jeschke M G, et al. What, how, and how much should patients with burns be fed?[J]. Surg Clin North Am, 2011, 91(3): 609-629. [4]Egerman M A, Glass D J. Signaling pathways controlling skeletal muscle mass[J]. Crit Rev Biochem Mol Biol, 2014, 49(1): 59-68. [5]柴家科. 严重烧伤后骨骼肌消耗的机制与治疗前景思考[J]. 中华烧伤杂志, 2009, 25(4): 243-245. [6]Tzika A A, Astrakas L G, Cao H, et al. Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma[J]. Int J Mol Med, 2008, 21(6): 825-832. [7]Wade C E, Mora A G, Shields B A, et al. Signals from fat after injury: plasma adipokines and ghrelin concentrations in the severely burned[J]. Cytokine, 2013, 61(1): 78-83. [8]O’Neill H M, Lally J S, Galic S, et al. AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice[J]. Diabetologia, 2014, 57(8): 1693-1702. [9]Niu Y, Yuan H, Fu L. Aerobic exercise’s reversal of insulin resistance by activating AMPKalpha-ACC-CPT1 signaling in the skeletal muscle of C57BL/6 mice[J]. Int J Sport Nutr Exerc Metab, 2010, 20(5): 370-380. [10]Bastin J. Regulation of mitochondrial fatty acid beta-oxidation in human: what can we learn from inborn fatty acid beta-?oxidation? deficiencies?[J]. Biochimie, 2014, 96: 113-120. [11]Zhou G, Sebhat I K, Zhang B B. AMPK activators--potential therapeutics for metabolic and other diseases[J]. Acta Physiol (Oxf), 2009, 196(1): 175-190. [12]Grahame-Hardie D. AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease[J]. J Intern Med, 2014, 276(6): 543-559. [13]王金霞, 任建功, 罗辉, 等. AMPK?2基因多态性与2型糖尿病及血清脂联素、颈动脉粥样硬化的关系[J]. 第三军医大学学报, 2012, 34(6): 530-533. [14]Zhang B B, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome[J]. Cell Metab, 2009, 9(5): 407-416. [15]Zungu M, Schisler J C, Essop M F, et al. Regulation of AMPK by the ubiquitin proteasome system[J]. Am J Pathol, 2011, 178(1): 4-11. [16]Merritt E K, Thalacker-Mercer A, Cross J M, et al. Increased expression of atrogenes and TWEAK family members after severe burn injury in nonburned human skeletal muscle[J]. J Burn Care Res, 2013, 34(5): e297-e304.

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