Acacetin attenuates diabetes-induced cardiomyopathy by inhibiting oxidative stress and energy metabolism via PPAR-α/AMPK pathway
Acacetin attenuates diabetes-induced cardiomyopathy by inhibiting oxidative stress and energy metabolism via PPAR-α/AMPK pathway
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Acacetin 通过 PPAR-α/AMPK 通路抑制氧化应激和能量代谢，从而减轻糖尿病引起的心肌病
DOI：
10.1016/j.ejphar.2022.174916
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发表时间：
2022
影响因子：
5
通讯作者：
Gang Li
中科院分区：
文献类型：
--
作者：
Fei Song;Yi-Jie Mao;Yu Hu;Shan-Shan Zhao;Ruiying Wang;Wei-Yin Wu;Gui-Rong Li;Yan Wang;Gang Li
糖尿病心肌病严重影响糖尿病患者的生活质量，严重者可导致心力衰竭和死亡。金合欢素是一种抗氧化剂和抗炎剂，在多种心血管疾病中被报道。然而，金合欢素对糖尿病性心肌病的作用尚不清楚。本研究采用体外和体内实验技术探讨金合欢素对糖尿病心肌病的治疗作用及其可能机制。在培养的新生大鼠心肌细胞和H9 C2心肌细胞中，金合欢素（0.3，1，3 μM）以浓度依赖性方式显示出对高糖诱导的损伤的有效保护作用。金合欢素可对抗高糖诱导的Bax增加以及Bcl-2、SOD 1和SOD 2的减少。在链脲佐菌素诱导的大鼠糖尿病心肌病模型中，用金合欢素前药（10 mg/kg，s.c.，b.i.d.）显著改善心功能，减轻心肌损伤，逆转血清MDA、Ang Ⅱ、IL-6、心肌Bax、IL-6水平的升高和血清SOD水平的降低，提示金合欢素可能通过抑制氧化应激、炎症反应和细胞凋亡发挥心肌保护作用。此外，体外和体内实验结果均显示，金合欢素可增加PPAR-α和pAMPK的表达，提示PPAR-α和pAMPK是金合欢素防治糖尿病心肌病的潜在靶点。本研究为金合欢素治疗糖尿病性心肌病提供了新的应用。
Diabetic cardiomyopathy seriously affects the life quality of diabetic patients and can lead to heart failure and death in severe cases. Acacetin was reported to be an anti-oxidant and anti-inflammatory agent in several cardiovascular diseases. However, the effect of acacetin on diabetic cardiomyopathy was not understood. This study was designed to explore the therapeutic effect of acacetin on diabetic cardiomyopathy and the potential mechanism within vitroandin vivoexperimental techniques. In cultured neonatal rat cardiomyocytes and H9C2 cardiac cells, acacetin (0.3, 1, 3 μM) showed effective protection against high glucose-induced injury in a concentration-dependent manner. Acacetin countered high glucose-induced increase of Bax and decrease of Bcl-2, SOD1, and SOD2. In streptozotocin-induced rat diabetic cardiomyopathy model, treatment with acacetin prodrug (10 mg/kg, s.c., b.i.d.) significantly improved the cardiac function and reduced myocardial injury, and reversed the increase of serum MDA, Ang Ⅱ, and IL-6 levels and myocardial Bax and IL-6, and the decrease of serum SOD, indicating that acacetin plays a cardioprotective effect by inhibiting oxidative stress, inflammation, and apoptosis. In addition, bothin vitroandin vivoexperimental results showed that acacetin increased the expression of PPAR-α and pAMPK, indicating that PPAR-α and pAMPK are potential targets of acacetin for the protection against diabetic cardiomyopathy. This study demonstrates the new application of acacetin for treating diabetic cardiomyopathy.