Naringin inhibits autophagy mediated by PI3K-Akt-mTOR pathway to ameliorate endothelial cell dysfunction induced by high glucose/high fat stress
Naringin inhibits autophagy mediated by PI3K-Akt-mTOR pathway to ameliorate endothelial cell dysfunction induced by high glucose/high fat stress
复制标题
柚皮苷抑制 PI3K-Akt-mTOR 通路介导的自噬，改善高糖/高脂应激引起的内皮细胞功能障碍。
DOI：
10.1016/j.ejphar.2020.173003
复制
发表时间：
2020-05-05
影响因子：
5
通讯作者：
Huang, Qiren
中科院分区：
文献类型：
--
作者：
Wang, Kun;Peng, Shengjia;Huang, Qiren
柚皮苷（naringin, Nar）作为一种类黄酮，具有降低血胆固醇、减少血栓形成和改善微循环等多种药理作用。然而，在高糖高脂（HG/HF）应激下，Nar对血管内皮细胞功能和自噬的影响在很大程度上尚不清楚。本研究旨在探讨Nar对人脐静脉内皮细胞（HUVECs）的影响，并确定这种影响是否与自噬有关。我们目前的研究结果表明，86 μ M的Nar抑制了自噬水平，并保护细胞免受HG/HF应激引起的功能障碍。此外，Nar增加了磷脂酰肌醇-3激酶（PI3K）、蛋白激酶B （Akt）和哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化水平。然而，经雷帕霉素（RAPA, 5 μ M，自噬诱导剂）、LY294002（10 μ M， PI3K抑制剂）和Akt抑制剂IV （0.5 μ M， Akt抑制剂）预处理后，部分削弱了Nar的保护作用，提示Nar的保护作用是通过激活PI3K-Akt- mtor通路抑制自噬来实现的。综上所述，Nar通过激活PI3K-Akt-mTOR通路抑制自噬，改善HG/HF应激下HUVECs的功能。该研究结果为HG/HF应激诱导的自噬提供了深入的见解，并表明Nar可能具有预防和治疗糖尿病血管病变的潜力。
As a flavonoid, naringin (Nar) has been shown to have multiple pharmacological effects including lowering blood cholesterol, reducing thrombus formation and improving microcirculation. However, effects of Nar on function and autophagy of vascular endothelial cells under high glucose and high fat (HG/HF) stress are largely unclear. This study was designed to investigate such effects of Nar in human umbilical vein endothelial cells (HUVECs) and to determine whether such effects are related to autophagy. Our present results show that 86 mu M of Nar inhibits the autophagy levels and protects the cells against the dysfunction induced by HG/HF stress. Moreover, Nar increases the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR). However, pretreatment with rapamycin (RAPA, 5 mu M, autophagy inducer), LY294002(10 mu M, PI3K inhibitor) and Akt inhibitor IV (0.5 mu M, Akt inhibitor) partially abrogates the protective effects of Nar, suggesting that the protective effects of Nar are achieved by activating the PI3K-Akt-mTOR pathway to inhibit autophagy. In conclusion, Nar improves the function of HUVECs under HG/HF stress through activating the PI3K-Akt-mTOR pathway to inhibit autophagy. The findings offer an insight into HG/HF stress-induced autophagy and indicate that Nar might have potential to prevent and treat the diabetic angiopathy.