Alpha-Linolenic Acid Exerts an Endothelial Protective Effect against High Glucose Injury via PI3K/Akt Pathway
Alpha-Linolenic Acid Exerts an Endothelial Protective Effect against High Glucose Injury via PI3K/Akt Pathway
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α-亚麻酸通过 PI3K/Akt 途径对高血糖损伤发挥内皮保护作用
DOI：
10.1371/journal.pone.0068489
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发表时间：
2013-07-05
期刊：
影响因子：
3.7
通讯作者：
Zhang, Haifeng
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Li, Rong;Zhang, Haifeng
越来越多的证据表明，膳食中的α-亚麻酸(ALA)对心血管有保护作用，但ALA对高糖损伤是否具有内皮保护作用及其可能的机制尚不清楚。链脲佐菌素诱导的糖尿病大鼠随机分为空白对照组(0.01%酒精)和丙氨酸(500µg/(kg·d)灌胃)，连续4周。人脐静脉内皮细胞(HUVECs)暴露于高糖(28 mmol/L)刺激48h。ALA显著改善糖尿病大鼠主动脉段ACh的浓度依赖性血管松弛，抑制血管内皮细胞炎症，表现为糖尿病大鼠血清可溶性P-选择素和细胞间黏附分子-1(ICAM-1)水平下降。此外，高糖诱导的HUVECs中P-选择素和ICAM-1的表达均显著增加，导致中性粒细胞与HUVECs的粘附性增强。ALA(50µm o l/L)使高糖培养的人脐静脉内皮细胞Akt磷酸化增加，P-选择素和细胞间黏附分子-1表达减弱，从而抑制中性粒细胞黏附，这些作用均被PI3K抑制剂LY294002和Wortmannin阻断。这些数据表明，ALA可抑制STZ诱导的糖尿病大鼠的内皮炎症反应，改善内皮功能。ALA抗高糖损伤的作用可能部分是通过PI3K/Akt途径实现的。
Mounting evidence has indicated that the cardiovascular protective effects of dietary alpha-linolenic acid (ALA), but whether ALA exerts an endothelial protective effect against high glucose injury and the underlying mechanisms remain largely unknown. Streptozocin-induced diabetic rats were randomized treated orally for 4 weeks with vehicle (0.01% alcohol) or ALA (500 µg/kg per day by gavage). Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (28 mmol/L) stimulation for 48 hours. ALA significantly improved concentration-dependent vasorelaxation to ACh in diabetic aortic segments and inhibited endothelial inflammation as evidenced by decreased soluble P-selectin and intercellular adhesion molecule-1 (ICAM-1) in diabetic rats. Furthermore, both P-selectin and ICAM-1 expression were increased significantly in high glucose-induced HUVECs, resulting in enhanced neutrophils adhesion to HUVECs compared with normal glucose group. Treatment with ALA (50 µmol/L) increased Akt phosphorylation, attenuated P-selectin and ICAM-1 expressions and thus inhibited neutrophils adhesion in HUVECs exposed to high glucose, all of which was blocked by the PI3K inhibitors LY294002 and wortmannin. These data indicates that ALA inhibits endothelial inflammation and improved endothelial function in STZ-induced diabetic rats. The anti-adhesive effect of ALA against high glucose injury may partially be mediated by the PI3K/Akt pathway.