Objective To study the effect of Astragalus polysaccharide (APS) on skeletal muscle mitochondria in mice with chronic fatigue.Methods Chronic fatigue model was established by endurance exercise procedure.Forty BALB/c mice were randomly divided into the sedentary group (SED), endurance exercise group (EXE), APS group (SED+APS), and endurance exercise with APS supplementation group (EXE+APS).The exercise capacity was evaluated by index of the forced swimming capacity and forelimb grip strength.The levels of MDA, LDH, SOD and GPx in both serum and skeletal muscle were detected.Expression levels of PGC-1α, MnSOD, p53, Atg7, LC3, and p62 were detected by Western blot.Expression levels of mitochondrial fusion/fission-related mRNAs were detected by qRT-PCR.Results The index of the forced swimming capacity and forelimb grip strength were significantly increased in EXE+APS group (P<0.05, P<0.01).There were moderate negative correlations between endurance capacity and serum LDH, serum MDA levels and muscle tissue MDA levels;and positive correlations between endurance capacity and serum GPx level.Meanwhile, compared with EXE group, the expression levels of oxidative stress-related protein MnSOD and p53 were significantly reduced in the EXE+APS group (P<0.05, P<0.05), while the mitochondrial biogenesis-related protein PGC-1α was significantly increased (P<0.01);and the autophagy-related protein Atg7 and LC3-Ⅱ/LC3-Ⅰ were significantly reduced (P<0.05, P<0.05), as the p62 was significantly increased (P<0.05).Compared with EXE group, the expression of Mnf-1 and Mnf-2 mRNAs was significantly higher in EXE+APS group (P<0.05, P<0.05), while Drp-1 mRNA was significantly lower (P<0.05).Conclusion APS could restore the exercise capacity in mice with chronic fatigue.The molecular mechanism underlying may involve reduction in oxidative stress, mitophagy restoration, mitochondrial biogenesis, and mitochondrial fusion/fission in skeletal muscles.%目的 观察黄芪多糖(APS)对慢性疲劳小鼠骨骼肌线粒体功能的影响及作用机制.方法 采用力竭性游泳方法构建慢性疲劳模型,将40只BALB/c小鼠随机分为空白对照组(SED组)、模型组(EXE组)、黄芪多糖对照组(SED+APS组)、黄芪多糖干预组(EXE+APS组).SED组:给予生理盐水灌胃,予以静坐;EXE组:给予生理盐水灌胃,予以力竭性运动;SED+APS组:给予APS灌胃,予以静坐处理;EXE+APS组:给予APS灌胃,予以力竭性运动.测试小鼠运动耐力,检测血清及骨骼肌内丙二醛(MDA)、乳酸脱氢酯(LDH)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)水平,Western blot法检测PGC-1α、MnSOD、p53、Atg7、LC3、p62水平,qRT-PCR法检测骨骼肌内Mfn-1、Mfn-2、Opa-1、Drp-1、Fis-1蛋白mRNA水平.结果 与EXE组相比,EXE+APS组的运动耐力及前肢握力均明显提高(P<0.05,P<0.01),且小鼠运动耐力与血清LDH、MDA及骨骼肌MDA呈负相关(P<0.05),与血清GPx呈正相关(P<0.05);与EXE组相比,EXE+APS组骨骼肌中的氧化应激相关蛋白MnSOD和p53水平下降(P<0.05),线粒体起源相关蛋白PGC-1α表达升高(P<0.01),自噬相关蛋白Atg7和LC3-Ⅱ/LC3-Ⅰ表达水平下降(P<0.05,P<0.01)、p62表达水平升高(P<0.05);与EXE组相比,EXE+APS组Mnf-1和Mnf-2 mRNA的表达水平升高(P<0.05),而Drp-1 mRNA的表达水平则下降(P<0.05).结论 黄芪多糖可提高慢性疲劳小鼠的运动耐力,其分子机制与降低组织内氧化应激水平,改善骨骼肌线粒体自噬、起源及线粒体融合-分裂有关.
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