Resveratrol Ameliorates Cardiac Dysfunction by Inhibiting Apoptosis via the PI3K/Akt/FoxO3a Pathway in a Rat Model of Diabetic Cardiomyopathy
Resveratrol Ameliorates Cardiac Dysfunction by Inhibiting Apoptosis via the PI3K/Akt/FoxO3a Pathway in a Rat Model of Diabetic Cardiomyopathy
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在糖尿病心肌病大鼠模型中，白藜芦醇通过 PI3K/Akt/FoxO3a 途径抑制细胞凋亡，从而改善心脏功能障碍。
DOI：
10.1097/fjc.0000000000000504
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发表时间：
2017-09-01
影响因子：
3
通讯作者：
Chen, Minsheng
中科院分区：
文献类型：
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作者：
Wu, Zhiye;Huang, Anqing;Chen, Minsheng
本研究旨在探讨白藜芦醇（RSV）对糖尿病心肌病（DCM）心功能的影响及其作用机制。高血糖诱导的细胞凋亡参与了DCM的病理变化。RSV处理抑制高糖诱导的新生大鼠心室肌细胞凋亡。此外，高葡萄糖降低细胞活力，阻止丝氨酸-苏氨酸激酶（Akt）和FoxO 3a磷酸化，并抑制FoxO 3a的细胞质易位。然而，这些细胞凋亡的影响被逆转10 μ M的RSV。PI 3 K抑制剂LY 294002在体外可消除RSV的保护作用。RSV（5或50 mg.kg（-1）.d（-1）口服8周）可预防链脲佐菌素诱导的糖尿病大鼠模型的心脏功能恶化和结构性心肌病，并减少糖尿病心肌细胞凋亡。此外，它恢复链脲霉素受损的Akt和FoxO 3a磷酸化（p-Akt和p-FoxO 3a），并抑制体内FoxO 3a的核转位。总之，这些数据表明RSV通过经由PI 3 K/Akt/FoxO 3a途径抑制细胞凋亡而具有针对DCM的治疗潜力。
The aim of this study was to explore the effect and mechanism of action of resveratrol (RSV) on cardiac function in diabetic cardiomyopathy (DCM). Hyperglycemia-induced apoptosis contributes to the pathogenic changes in DCM. RSV treatment inhibited high glucose-induced apoptosis of neonatal rat ventricular myocytes. Additionally, high glucose decreased cell viability, prevented serine-threonine kinase (Akt) and FoxO3a phosphorylation, and suppressed cytoplasmic translocation of FoxO3a. However, these effects of apoptosis were reversed by 10 mu M of RSV. The PI3K inhibitor LY294002 abolished the RSV protective effect in vitro. RSV (5 or 50 mg.kg(-1).d(-1) orally for 8 weeks) prevented the deterioration of cardiac function and structural cardiomyopathy in a streptozotocin-induced rat model of diabetes and reduced apoptosis in diabetic myocardium. Furthermore, it restored streptozotocin-impaired phosphorylation of Akt and FoxO3a (p-Akt and p-FoxO3a) and suppressed nuclear translocation of FoxO3a in vivo. Together, these data indicate that RSV has therapeutic potential against DCM by inhibiting apoptosis via the PI3K/Akt/FoxO3a pathway.