Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway.
Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway.
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DOI：
10.3892/ijmm.2016.2549
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发表时间：
2016-05
影响因子：
5.4
通讯作者：
Chen LM
中科院分区：
文献类型：
--
作者：
Guan Y;Cui ZJ;Sun B;Han LP;Li CJ;Chen LM
氧化应激在糖尿病肌病的发病机制中起着关键作用。南蛇藤酚具有广泛的健康益处，包括抗氧化、抗炎和抗肿瘤作用。我们推测雷公藤红素可能在糖尿病大鼠的骨骼肌中发挥抗氧化作用。本研究采用分光光度法测定MnSOD活性。通过蛋白质印迹分析评估蛋白质水平，并通过RT-qPCR定量mRNA含量。我们首次发现糖尿病患者骨骼肌中AMPK、PGC 1 α、SIRT 3和MnSOD水平均降低。患有糖尿病的雄性大鼠也用媒介物或雷公藤红素以1、3和6 mg/kg/天治疗8周。组织学分析表明，雷公藤红素3和6 mg/kg剂量组骨骼肌的损伤程度减轻，酶联免疫吸附试验（ELISA）测定丙二醛（MDA）水平降低，谷胱甘肽（GSH）水平升高。提高MnSOD的活性，增加AMPK的磷酸化水平，增加PGC 1 α和Sirt 3的表达。提示糖尿病患者骨骼肌AMPK、PGC 1 α、SIRT 3和MnSOD表达降低。雷公藤红素通过调节AMPK-PGC 1 α-SIRT 3信号通路发挥抗氧化作用。
Oxidative stress plays a key role in the pathogenesis of diabetic myopathy. Celastrol provides a wide range of health benefits, including antioxidant, anti-inflammatory and antitumor effects. We hypothesized that celastrol may exert an antioxidant effect in the skeletal muscle of diabetic rats. In the present study, MnSOD activity was determined by spectrophotometry. The protein levels were evaluated by western blot analysis and mRNA content was quantified by RT-qPCR. We firstly found that the levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator 1α (PGC1α), silent mating-type information regulation 2 homolog 3 (SIRT3) and manganese superoxide dismutase (MnSOD) were all decreased in the skeletal muscle of diabetic patients. Male rats with diabetes were also treated with the vehicle or with celastrol at 1, 3 and 6 mg/kg/day for 8 weeks. The administration of celastrol at 3 and 6 mg/kg attenuated the deterioration of skeletal muscle, as shown by histological analysis, decreased the malondialdehyde (MDA) level and increased the glutathione (GSH) level assayed by enzyme-linked immunosorbent assay (ELISA) method. It also enhanced the enzyme activity and increased the expression of MnSOD, and increased the AMPK phosphorylation level, as well as PGC1α and Sirt3 expression. The findings of our study suggest that the expression of AMPK, PGC1α, SIRT3 and MnSOD are decreased in the skeletal muscle of diabetic patients. Celastrol exerted antioxidant effects on skeletal muscle partly by regulating the AMPK-PGC1α-SIRT3 signaling pathway.