Astragaloside IV alleviates myocardial damage induced by type 2 diabetes via improving energy metabolism

Astragaloside IV alleviates myocardial damage induced by type 2 diabetes via improving energy metabolism
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黄芪甲苷通过改善能量代谢减轻2型糖尿病引起的心肌损伤

DOI:
10.3892/mmr.2019.10716
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发表时间:
2019-10
期刊:
Mol Med Rep
影响因子:
--
通讯作者:
Wang Hongxin
Wang Hongxin
中科院分区:
其他
文献类型:
--
作者:
Zhang Zhen;Wang Hongxin

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本研究旨在从能量代谢角度探讨黄芪甲苷(ASIV)对2型糖尿病心肌损伤的保护作用及其机制。检测糖尿病大鼠血糖、血流动力学指标、左心室重量/心脏重量(LVW/HW)、左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)及细胞存活率。采用Western blot、PCR、苏木精-伊红和TUNEL染色、流式细胞术和ELISA检测心肌细胞损伤指标心钠素(ANP)、脑钠素(BNP)、细胞色素C(Cyt C)、caspase-3、裂解型caspase-3和凋亡率,能量代谢指标ATP/AMP和ADP/AMP,并检测心肌细胞凋亡率。和iii)能量代谢相关途径蛋白,例如过氧化物酶体增殖物激活受体γ共激活因子1-α(PGC-1α)和核呼吸因子1(NRF 1)。结果显示,糖尿病组和高糖组的血糖、LVW/HW、LVSP、LVEDP和心肌细胞损伤指标(ANP、BNP、Cyt C和caspase-3)均升高,ASIV可降低上述指标。模型组NRF-1和PGC-1α表达明显改变,ASIV治疗后NRF-1和PGC-1α表达明显改善。ASIV还能逆转模型组的能量代谢异常。结果表明,ASIV可通过调节PGC-1α和NRF 1的释放来调节能量代谢,挽救糖尿病引起的能量代谢异常,从而减轻糖尿病心肌病引起的心肌损害。
The aim of the present study was to evaluate the protective effect and mechanism of Astragaloside IV (ASIV) on myocardial injury induced by type 2 diabetes, with a focus on energy metabolism. Blood glucose, the hemodynamic index, left ventricular weight/heart weight (LVW/HW), the left ventricular systolic pressure (LVSP), the left ventricular end diastolic pressure (LVEDP) and cell survival rate were measured in streptozotocin-induced diabetes model rats. Western blot analysis, PCR, hematoxylin-eosin and TUNEL staining, flow cytometry and ELISA were used to detect: i) Cardiomyocyte damage indicators such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cytochrome c (Cyt C), caspase-3, cleaved caspase-3 and the apoptotic rate; ii) energy metabolism indicators such as ATP/AMP and ADP/AMP; and iii) energy metabolism associated pathway proteins such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and nuclear respiratory factor 1 (NRF1). The present demonstrated increased blood glucose, LVW/HW, LVSP, LVEDP and the cardiomyocyte damage indicators (ANP, BNP, Cyt C and caspase-3), in the diabetic and high glucose-treated groups, which were decreased by ASIV. The expression of NRF-1 and PGC-1α significantly changed in the model group and was markedly improved following ASIV treatment. Furthermore, the abnormal energy metabolism in the model group was reversed by ASIV. According to the results, ASIV can regulate energy metabolism by regulating the release of PGC-1α and NRF1 to rescue the abnormal energy metabolism caused by diabetes mellitus, thus decreasing the myocardial damage caused by diabetic cardiomyopathy.
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