Berberine protects against palmitate-induced endothelial dysfunction: involvements of upregulation of AMPK and eNOS and downregulation of NOX4.
Berberine protects against palmitate-induced endothelial dysfunction: involvements of upregulation of AMPK and eNOS and downregulation of NOX4.
复制标题
ber碱可预防棕榈酸酯引起的内皮功能障碍：AMPK和ENOS上调的参与以及NOX4的下调。
DOI：
10.1155/2013/260464
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发表时间：
2013
影响因子：
4.6
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Zhang M;Wang CM;Li J;Meng ZJ;Wei SN;Li J;Bucala R;Li YL;Chen L
内皮功能障碍是糖尿病心血管并发症发生的关键因素。小檗碱可改善糖尿病引起的内皮功能障碍。然而，潜在的机制仍不清楚。本研究旨在探讨小檗碱对棕榈酸诱导的人脐静脉内皮细胞（HUVECs）内皮功能障碍的保护作用及其机制。MTT法检测HUVECs细胞活力。测定培养的HUVECs上清液中一氧化氮（NO）水平和活性氧（ROS）的产生。RT-PCR检测内皮型一氧化氮合酶（eNOS） mRNA表达水平，分析eNOS、p-eNOS、Akt、p-Akt、AMPK、p-AMPK、NADPH氧化酶（NOX4）蛋白表达水平。结果表明，小檗碱显著提高NO水平，减少ROS的产生。在小檗碱处理的huvec中，eNOS蛋白表达显著升高，NOX4蛋白表达显著降低。此外，小檗碱上调了棕榈酸处理的huvec中AMPK和p-AMPK的蛋白表达，但对Akt的水平没有影响。因此，小檗碱通过上调eNOS表达和下调NOX4表达来改善棕榈酸盐诱导的内皮功能障碍。小檗碱的这种调节作用可能与AMPK的激活有关。
Endothelial dysfunction is a critical factor during the initiation of cardiovascular complications in diabetes. Berberine can ameliorate endothelial dysfunction induced by diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the protective effect and mechanism of berberine on palmitate-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). The cell viability of HUVECs was determined by MTT assays. Nitric oxide (NO) level and production of reactive oxygen species (ROS) were determined in supernatants or in the cultured HUVECs. The mRNA level of endothelial nitric oxide synthase (eNOS) was measured by RT-PCR, and the protein levels of eNOS, p-eNOS, Akt, p-Akt, AMPK, p-AMPK, and NADPH oxidase (NOX4) were analyzed. The results demonstrated that berberine significantly elevated NO levels and reduced the production of ROS. The expressions of eNOS were significantly increased, while NOX4 protein expression was decreased in berberine-treated HUVECs. Moreover, berberine upregulated the protein expression of AMPK and p-AMPK in palmitate-treated HUVECs, but had no effect on the levels of Akt. Therefore, berberine ameliorates palmitate-induced endothelial dysfunction by upregulating eNOS expression and downregulating expression of NOX4. This regulatory effect of berberine may be related to the activation of AMPK.