Gao Hong-Li, Yu Xiao-Jing, Hu Han-Bo, Yang Qian-Wen, Liu Kai-Li, Chen Yan-Mei, Zhang Yan, Zhang Dong-Dong, Tian Hua, Zhu Guo-Qing, Qi Jie, Kang Yu-Ming
Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China.
Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
Cardiovasc Toxicol. 2021 Sep;21(9):721-736. doi: 10.1007/s12012-021-09662-1. Epub 2021 Jun 2.
Apigenin, identified as 4', 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.
芹菜素，即4'，5，7-三羟基黄酮，是一种天然黄酮类化合物，具有许多有趣的药理活性和营养保健潜力，包括抗炎和抗氧化功能。慢性低度炎症和氧化应激参与了高血压及高血压诱发的心脏肥大的发生和发展过程。然而，芹菜素是否通过调节下丘脑室旁核（PVN）中烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶依赖性活性氧（ROS）生成和炎症来改善高血压和心脏肥大尚未见报道。本研究旨在探讨芹菜素对自发性高血压大鼠（SHR）高血压的影响及其可能的中枢作用机制。将SHR和Wistar-Kyoto（WKY）大鼠随机分组，通过渗透微型泵（20μg/h）双侧PVN注入芹菜素或载体（人工脑脊液），持续4周。结果显示，PVN注入芹菜素后，平均动脉压（MAP）、心率、血浆去甲肾上腺素（NE）、肾脏中的β1受体、心室组织中蛋白激酶A（PKA）的磷酸化水平以及心脏肥大、血管周围纤维化、心脏氧化应激水平、PVN氧化应激水平、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）、诱导型一氧化氮合酶（iNOS）、单核细胞趋化蛋白1（MCP-1）、酪氨酸羟化酶（TH）、NOX2和NOX4均降低，而PVN中白细胞介素10（IL-10）、超氧化物歧化酶1（铜/锌超氧化物歧化酶）和谷氨酸脱羧酶67-kDa亚型（GAD67）水平升高。这些结果表明，芹菜素可改善SHR的高血压和心脏肥大，这与PVN中NADPH氧化酶依赖性ROS生成和炎症的下调有关。
