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.
Department of Cardiovascular Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Neurosci Bull. 2020 Apr;36(4):385-395. doi: 10.1007/s12264-019-00435-z. Epub 2019 Oct 22.
Toll-like receptor 4 (TLR4) and cellular Src (c-Src) 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 long-term 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.
Toll 样受体 4（TLR4）和细胞Src（c-Src）与高血压中的炎症细胞因子和氧化应激密切相关，因此我们设计了这项研究来探讨 c-Src 在 TLR4 信号通路在盐诱导高血压中的作用机制中的确切作用。盐敏感大鼠给予高盐饮食 10 周以诱导高血压。这导致 TLR4、激活的 c-Src、促炎细胞因子、氧化应激和动脉压升高。将 TLR4 阻滞剂注入下丘脑室旁核（PVN）可降低激活的 c-Src，而 c-Src 抑制剂的微注射可减弱 PVN 核因子-κB、促炎细胞因子和氧化应激水平。我们的研究结果表明，长期高盐饮食会增加 PVN 中的 TLR4 表达，从而促进 c-Src 的激活，上调促炎细胞因子的表达，并导致活性氧的过度产生。因此，抑制中枢 c-Src 活性可能是治疗高血压的新靶点。
