Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Int J Cardiol. 2013 Aug 10;167(3):936-42. doi: 10.1016/j.ijcard.2012.03.090. Epub 2012 Mar 31.
Circulating endothelial microparticles (EMPs) lead to endothelial dysfunction by increasing oxidative stress. Berberine has a beneficial effect on endothelial function, but no data are available on the EMP-mediated oxidative stress. The present study tests the hypothesis that berberine contributes to the improvement of endothelial function in humans via inhibiting EMP-mediated oxidative stress in vascular endothelium.
Twelve healthy subjects received a 1-month berberine therapy and eleven healthy subjects served as control. Endothelium-dependent and -independent function in the brachial artery was assessed by flow-mediated vasodilation (FMD) and sublingual nitroglyceride-mediated vasodilation (NMD). Circulating EMPs and serum malondialdehyde (MDA) were measured before and after therapy. Furthermore, in vitro human umbilical vein endothelial cells (HUVECs) were stimulated by EMPs with or without presence of anti-oxidant compound apocynin or berberine. Intracellular reactive oxygen species (ROS), nitric oxide (NO) production and NADPH oxidase 4 (Nox4) protein expressions were examined, respectively.
The levels of serum MDA and circulating CD31+/CD42- MPs were significantly reduced in the berberine group compared with the control group, which were associated with improvement of FMD. The EMPs in vitro facilitated ROS production and Nox4 protein expression and reduced NO synthesis in HUVECs. These alterations can be reversed by the presence of apocynin or berberine, respectively.
The present study demonstrated for the first time that EMP-induced upregulation of Nox4 expression may enhance ROS production in HUVECs. Berberine treatment contributes to the amelioration of endothelial function through a partially reducing oxidative stress of vascular endothelium induced by circulating CD31+/CD42- microparticles in humans.
循环内皮微粒（EMP）通过增加氧化应激导致内皮功能障碍。小檗碱对内皮功能有有益的影响，但没有关于 EMP 介导的氧化应激的数据。本研究通过抑制血管内皮中 EMP 介导的氧化应激，检验小檗碱通过改善内皮功能的假说。
12 名健康受试者接受了 1 个月的小檗碱治疗，11 名健康受试者作为对照。肱动脉内皮依赖性和非依赖性功能通过血流介导的血管扩张（FMD）和舌下硝酸甘油介导的血管扩张（NMD）进行评估。治疗前后测量循环 EMP 和血清丙二醛（MDA）。此外，用人脐带静脉内皮细胞（HUVEC）体外刺激 EMP，并分别用抗氧化剂化合物 apocynin 或小檗碱存在与否进行刺激。分别检测细胞内活性氧（ROS）、一氧化氮（NO）产生和 NADPH 氧化酶 4（Nox4）蛋白表达。
与对照组相比，小檗碱组血清 MDA 和循环 CD31+/CD42- MPs 水平显著降低，与 FMD 改善相关。体外 EMP 促进了 HUVEC 中 ROS 产生和 Nox4 蛋白表达，并减少了 NO 的合成。这些变化可以分别通过 apocynin 或小檗碱的存在而逆转。
本研究首次证明 EMP 诱导的 Nox4 表达上调可能增强 HUVEC 中的 ROS 产生。小檗碱治疗通过部分减少循环 CD31+/CD42- 微粒诱导的血管内皮氧化应激，有助于改善内皮功能。
