Bai Juan, Yu Xiao-Jing, Liu Kai-Li, Wang Fang-Fang, Li Hong-Bao, Shi Xiao-Lian, Zhang Yan, Huo Chan-Juan, Li Xiang, Gao Hong-Li, Qi Jie, Liu Jin-Jun, Zhu Guo-Qing, Chen Wen-Sheng, Cui Wei, Kang Yu-Ming
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.
Toxicol Lett. 2017 Nov 5;281:1-9. doi: 10.1016/j.toxlet.2017.08.018. Epub 2017 Aug 24.
Excessive oxidative stress and inflammation in hypothalamic paraventricular nucleus (PVN) are implicated in the pathogenesis of hypertension. It is reported that tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2(Nrf2)-inducer, has a variety of pharmacological activities such as anti-oxidation and anti-inflammatory effect. The objective of this study was to investigate the effects of tBHQ in high salt induced hypertension and to identify whether the beneficial effects were induced by inhibiting PVN oxidative stress and inflammation. Male Sprague-Dawley rats were fed with high salt diet (HS, 8% NaCl) or normal salt diet (NS, 0.3% NaCl). These rats were administration of tBHQ (150mg/kg/d) by oral gavage for 16 weeks. Our results showed that high salt intake resulted in higher mean arterial pressure, cardiac hypertrophy as well as increased plasma level of norepinephrine and interleukin (IL)-1β, IL-6 compared with NS rats. It increased PVN level of reactive oxygen species, gp91, IL-1β, IL-6, p-IKKβ and nuclear factor-kappa B (NF-κB) activity, decreased PVN level of Nrf2 and Cu/Zn-SOD. Chronic administration of tBHQ significantly attenuated these changes in HS rats. These data suggest that the protective effects of tBHQ in salt induced hypertension are partly due to inhibiting oxidative stress and inflammation in PVN.
下丘脑室旁核(PVN)中过度的氧化应激和炎症与高血压的发病机制有关。据报道,叔丁基对苯二酚(tBHQ)作为一种核因子红细胞2相关因子2(Nrf2)诱导剂,具有多种药理活性,如抗氧化和抗炎作用。本研究的目的是探讨tBHQ对高盐诱导高血压的影响,并确定其有益作用是否通过抑制PVN氧化应激和炎症而产生。将雄性Sprague-Dawley大鼠喂以高盐饮食(HS,8% NaCl)或正常盐饮食(NS,0.3% NaCl)。通过口服灌胃给予这些大鼠tBHQ(150mg/kg/d),持续16周。我们的结果显示,与NS大鼠相比,高盐摄入导致平均动脉压升高、心脏肥大以及血浆去甲肾上腺素和白细胞介素(IL)-1β、IL-6水平升高。它增加了PVN中活性氧、gp91、IL-1β、IL-6、p-IKKβ水平以及核因子κB(NF-κB)活性,降低了PVN中Nrf2和铜/锌超氧化物歧化酶(Cu/Zn-SOD)水平。长期给予tBHQ可显著减轻HS大鼠的这些变化。这些数据表明,tBHQ对盐诱导高血压的保护作用部分归因于抑制PVN中的氧化应激和炎症。