Sulistyowati Erna, Jan Ren-Long, Liou Shu-Fen, Chen Ying-Fu, Wu Bin-Nan, Hsu Jong-Hau, Yeh Jwu-Lai
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Faculty of Medicine, University of Islam Malang, Malang city, East Java, Indonesia.
J Tradit Complement Med. 2019 Jun 24;10(4):378-388. doi: 10.1016/j.jtcme.2019.06.003. eCollection 2020 Jul.
, and decoction (CJID) is efficacious for hypertension. NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-induced reactive oxygen species (ROS) generation modulates nuclear factor kappa B (NF-κB) activation and thus mediates hypertension-induced vascular remodeling. This research aims to investigate the anti-remodeling effect of CJID through the mechanism of NOXs-ROS-NF-κB pathway in spontaneously hypertensive rats (SHRs).
CJID was orally administered once a day for five weeks in SHRs and normotensive-WKY (Wistar Kyoto) rats. All rats were sacrificed at the end of study and different assays were performed to determine whether CJID ameliorates vascular remodeling in SHRs, such as histological examination; lactate dehydrogenase (LDH), nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) assays; superoxide and hydrogen peroxide (HO) generation assays, immunohistochemistry and immunofluorescence assays. . Changes in levels of inducible nitric oxide synthase (iNOS), NF-κB-p65, NF-κB inhibitor alpha/IκBα (inhibitory kappa B- alpha), phosphorylation of IκBα (p-IκBα) and NOX1, NOX2, NOX4 in the thoracic aorta were determined.
Vascular remodeling indicators, media thickness, collagen and elastic accumulation in the thoracic aorta, of SHRs-treated CJID were attenuated. Redox homeostasis, aortic superoxide and hydrogen peroxide generation were decreased in SHRs-treated group. Aortic iNOS, p-IκBα, NF-κB-p65 and NOX1, NOX2, NOX4 expressions were suppressed.
CJI treatment diminishes oxidative stress response in the thoracic aorta of SHRs via regulation of NOXs-ROS-NF-κB signaling pathway. These findings indicate that CJI possess protective effect against hypertension-induced vascular remodeling in SHRs.
柴芩温胆汤（CJID）对高血压有效。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）诱导的活性氧（ROS）生成调节核因子κB（NF-κB）激活，从而介导高血压诱导的血管重塑。本研究旨在通过NOXs-ROS-NF-κB途径机制探讨柴芩温胆汤对自发性高血压大鼠（SHRs）的抗重塑作用。
柴芩温胆汤每日一次口服给药，持续五周，用于治疗SHRs和血压正常的WKY（Wistar Kyoto）大鼠。在研究结束时处死所有大鼠，并进行不同检测以确定柴芩温胆汤是否改善SHRs的血管重塑，如组织学检查；乳酸脱氢酶（LDH）、一氧化氮（NO）、丙二醛（MDA）和超氧化物歧化酶（SOD）检测；超氧化物和过氧化氢（HO）生成检测、免疫组织化学和免疫荧光检测。测定胸主动脉中诱导型一氧化氮合酶（iNOS）、NF-κB-p65、NF-κB抑制剂α/IκBα（抑制性κB-α）、IκBα磷酸化（p-IκBα）以及NOX1、NOX2、NOX4水平的变化。
接受柴芩温胆汤治疗的SHRs的血管重塑指标，如胸主动脉中膜厚度、胶原蛋白和弹性蛋白积累均有所减轻。接受治疗的SHRs组的氧化还原稳态、主动脉超氧化物和过氧化氢生成减少。主动脉iNOS、p-IκBα、NF-κB-p65以及NOX1、NOX2、NOX4表达受到抑制。
柴芩温胆汤治疗通过调节NOXs-ROS-NF-κB信号通路减轻SHRs胸主动脉的氧化应激反应。这些发现表明柴芩温胆汤对SHRs高血压诱导的血管重塑具有保护作用。
