Blockade of c-Src Within the Paraventricular Nucleus Attenuates Inflammatory Cytokines and Oxidative Stress in the Mechanism of the TLR4 Signal Pathway in Salt-Induced Hypertension  

作　　者：Qing Yang Xiao-Jing Yu Qing Su Qiu-Yue Yi Xin-Ai Song Xiao-Lian Shi Hong-Bao Li Jie Qi Guo-Qing Zhu Yu-Ming Kang 

机构地区：[1]Department of Physiology and Pathophysiology,Xi'an Jiaotong University School of Basic Medical Sciences,Key Laboratory of Environment and Genes Related to Diseases of the Ministry of Education,Xi'an Jiaotong University,Xi’an 710061,China [2]Department of Cardiovascular Surgery,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China [3]Department of Pharmacology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an 710061,China [4]Key Laboratory of Cardiovascular Disease and Molecular Intervention,Department of Physiology,Nanjing Medical University,Nanjing 210029,China

出　　处：《Neuroscience Bulletin》2020年第4期385-395,共11页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (81770426, 81600333, 81600330, and 81800373);China Postdoctoral Science Foundation (2016M602835);Shaanxi Postdoctoral Science Foundation (2016BSHEDZZ91).

摘　　要：Toll-like receptor 4 (TLR4) and cellular Src (cSrc) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension. Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension. This resulted in higher levels of TLR4, activated c-Src, pro-inflammatory cytokines, oxidative stress, and arterial pressure. Infusion of a TLR4 blocker into the hypothalamic paraventricular nucleus (PVN) decreased the activated c-Src, while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B, pro-inflammatory cytokines, and oxidative stress. Our findings suggest that a longterm high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src, which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species.Therefore, inhibiting central c-Src activity may be a new target for treating hypertension.

关 键 词：TOLL-LIKE receptor 4 Cellular Src Inflammatory cytokines Oxidative stress HYPOTHALAMIC PARAVENTRICULAR nucleus Salt-induced hypertension 

分 类 号：R544.1[医药卫生—心血管疾病] R741[医药卫生—内科学]