Jiangxi Provincial Institute of Hypertension, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang 330006, China.
Toxicol In Vitro. 2020 Jun;65:104817. doi: 10.1016/j.tiv.2020.104817. Epub 2020 Mar 2.
Iron overload causes vascular endothelium damage. It has been thought to relate excessive reactive oxygen species (ROS) generation. Tetramethylpyrazine (TMP), an active ingredient of Ligusticum chuanxiong Hort, protects various cells by inhibiting oxidative stress and cascade reaction of apoptosis. However, whether TMP can increase DDAHII activity and expression against endothelial cell damage induced by iron overload, and the protective mechanism has not been elucidated. In this study, 50 μM iron dextran and 25 μM TMP were used to co-treat HUVECs for 48 h. TMP could increase cell viability and decrease LDH activity, enhance DDAHII expression and activity, p-eNOS/eNOS ratio, NO content, and reduce ADMA level. TMP also showed a strong antioxidant activity with inhibited ROS generation and oxidative stress. Moreover, TMP attenuated mitochondrial membrane potential loss, inhibited mitochondrial permeability transition pore openness, and decreased apoptosis induced by iron overload. While mentioned above, the protective effects of TMP were abolished with the addition of pAD/DDAHII-shRNA. The effects of TMP against iron overload were similar to the positive control groups, L-arginine, a competitive substrate of ADMA, or edaravone, free radical scavenger. These results signify that TMP alleviated iron overload damage in vascular endothelium via ROS/ADMA/ DDAHII/eNOS/NO pathway.
铁过载导致血管内皮细胞损伤。人们认为这与过量的活性氧（ROS）生成有关。川芎嗪（TMP）是川芎的一种有效成分，通过抑制氧化应激和细胞凋亡级联反应来保护各种细胞。然而，TMP 是否可以增加 DDAHII 活性和表达，以抵抗铁过载引起的内皮细胞损伤，以及其保护机制尚未阐明。在这项研究中，用 50 μM 右旋糖酐铁和 25 μM TMP 共同处理 HUVECs 48 小时。TMP 可以增加细胞活力，降低 LDH 活性，增强 DDAHII 的表达和活性、p-eNOS/eNOS 比值、NO 含量，并降低 ADMA 水平。TMP 还表现出强大的抗氧化活性，抑制 ROS 生成和氧化应激。此外，TMP 减轻了铁过载引起的线粒体膜电位丧失、抑制了线粒体通透性转换孔的开放，并减少了细胞凋亡。虽然提到了上述内容，但加入 pAD/DDAHII-shRNA 后，TMP 的保护作用被消除。TMP 对铁过载的作用与阳性对照组相似，即 L-精氨酸（ADMA 的竞争性底物）或依达拉奉（自由基清除剂）。这些结果表明，TMP 通过 ROS/ADMA/ DDAHII/eNOS/NO 途径减轻血管内皮细胞的铁过载损伤。
