Astragaloside IV reverses simvastatin-induced skeletal muscle injury by activating the AMPK-PGC-1α signalling pathway
Astragaloside IV reverses simvastatin-induced skeletal muscle injury by activating the AMPK-PGC-1α signalling pathway
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黄芪甲苷通过激活AMPK-PGC-1α信号通路逆转辛伐他汀诱导的骨骼肌损伤
DOI：
10.1002/ptr.6593
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发表时间：
2020-05-01
影响因子：
7.2
通讯作者：
Hu, Xu-Guang
中科院分区：
文献类型：
--
作者：
Jiang, Bing;Yang, Yu-Jiao;Hu, Xu-Guang
本研究探讨黄芪甲苷IV对他汀类药物引起的骨骼肌能量代谢紊乱的影响，并探讨其可能的机制。高脂饮食喂养的载脂蛋白E敲除（ApoE（-/-））小鼠进行有氧运动，并通过灌胃给予辛伐他汀、辛伐他汀+曲美他嗪或辛伐他汀+黄芪甲苷IV。治疗结束时，通过挂格测试、前肢握力测试和跑步耐力测试评估运动表现。此外，还测量了血浆脂质和肌酸激酶浓度。处死后，用腓肠肌评估肌肉形态，并通过测定乳酸浓度以及三磷酸腺苷和糖原的储存能力来评估能量代谢。通过测量线粒体复合物 III 和柠檬酸合酶活性以及膜电位来评估线粒体功能。此外，通过测定过氧化氢水平来评估氧化应激。最后，我们利用蛋白质印迹和逆转录聚合酶链反应，探讨了黄芪甲苷IV减轻辛伐他汀引起的肌肉损伤的机制。我们的结果表明，黄芪甲苷 IV 可以逆转辛伐他汀引起的肌肉损伤，而不影响辛伐他汀的降脂作用。此外，黄芪甲苷还能促进AMPK磷酸化，激活PGC-1α，上调NRF1表达，增强能量代谢，抑制骨骼肌细胞凋亡。
In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. High-fat diet-fed apolipoprotein E knockout (ApoE(-/-)) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test. Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin-induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin-induced muscle injury without affecting the lipid-lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC-1 alpha, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis.