Icariin (ICA), as a flavonoid glycoside, is associated with the improvement of vascular complications in diabetes. However, its protective mechanisms remain to be well‐established. Here, we tested the hypothesis that ICA attenuates vascular endothelial dysfunction by inhibiting endoplasmic reticulum (ER) stress in type 1 diabetes. In streptozotocin‐induced diabetic rats, ICA positively affected acetylcholine‐induced vasodilation and phenylephrine‐induced vasoconstriction in aortas. ICA treatment significantly attenuated ER stress in diabetic rats and high‐glucose induced human umbilical vein endothelial cells. Incubation with ICA in vitro attenuated vascular reactivity in diabetic rats, which was blocked by the ER stress inducer, and peroxisome proliferator‐activated receptor α (PPARα), sirtuin1 (Sirt1), or AMP‐activated protein kinase‐α (AMPKα) inhibitors. Western blot showed that ICA activated the PPARα/Sirt1/AMPKα pathway, which contributed to reducing ER stress and activating endothelial nitric oxide synthase in vivo and vitro. Our results implicate that ICA normalizes ER stress to attenuate endothelial dysfunction by the regulation of the PPARα/Sirt1/AMPKα pathway.

中文翻译：

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淫羊藿苷通过 PPARα/Sirt1/AMPKα 通路抑制 ER 应激来改善 1 型糖尿病大鼠的内皮功能障碍。

淫羊藿苷 (ICA) 作为一种黄酮苷，与改善糖尿病血管并发症有关。然而，其保护机制仍有待完善。在这里，我们测试了 ICA 通过抑制 1 型糖尿病中的内质网 (ER) 应激来减轻血管内皮功能障碍的假设。在链脲佐菌素诱导的糖尿病大鼠中，ICA 对乙酰胆碱诱导的主动脉血管舒张和苯肾上腺素诱导的血管收缩产生积极影响。ICA 治疗显着减弱糖尿病大鼠和高糖诱导的人脐静脉内皮细胞的 ER 应激。与 ICA 体外孵育减弱了糖尿病大鼠的血管反应性，这被 ER 应激诱导剂和过氧化物酶体增殖物激活受体 α (PPARα)、sirtuin1 (Sirt1)、或 AMP 活化蛋白激酶-α (AMPKα) 抑制剂。蛋白质印迹表明 ICA 激活了 PPARα/Sirt1/AMPKα 通路，这有助于减少 ER 应激并激活体内外内皮一氧化氮合酶。我们的结果表明 ICA 通过调节 PPARα/Sirt1/AMPKα 通路使内质网应激正常化以减轻内皮功能障碍。