Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA.
Acta Physiol (Oxf). 2018 Feb;222(2). doi: 10.1111/apha.12963. Epub 2017 Oct 23.
Accumulating evidence suggests that orexin signalling is involved in the regulation of blood pressure and cardiovascular function. However, the underlying mechanisms are not clear. Here, we test the hypothesis that upregulated orexin A signalling in the paraventricular nucleus (PVN) increases sympathetic nerve activity (SNA) through stimulating expression of proinflammatory cytokines (PICs).
In vivo sympathetic nerve recordings were performed to test the impact of PVN orexin signalling on sympathetic outflow in Sprague Dawley (SD) rats. Real-time PCR was carried out to assess effects of central administration of orexin A on PVN PICs expression in SD rats. To test whether orexin A-induced increases in PICs were exclusively mediated by orexin receptor 1 (OX1R), OX1R-expressing PC12 (PC12-OX1R) cells were incubated with different dose of orexin A, and then, PICs mRNA and immunoreactivity were measured.
Orexin A microinjection (25 pmol) into the PVN significantly increased splanchnic SNA (93.5%) and renal SNA (83.3%) in SD rats, and these increases were attenuated by OX1R antagonist SB408124. Intracerebroventricular injection of orexin A (0.2 nmol) into SD rats increased mRNA levels of PICs including IL-1-β (2.7-fold), IL-6 (1.7-fold) and TNF-α (1.5-fold), as well as Fra1 (1.6-fold) in the PVN. Orexin A treatment in PC12-OX1R cells resulted in a dose- and time-dependent increase in the expression of PICs and Fra1, a subunit of AP1 transcriptional factor. The increase in the PICs was blocked by AP1 blocker curcumin.
Paraventricular nucleus orexin system activation is involved in SNA regulation maybe through triggering AP1-PICs pathway.
越来越多的证据表明，食欲素信号参与了血压和心血管功能的调节。然而，其潜在机制尚不清楚。在这里，我们验证了一个假设，即室旁核（PVN）中上调的食欲素 A 信号通过刺激促炎细胞因子（PICs）的表达来增加交感神经活动（SNA）。
在 Sprague Dawley（SD）大鼠中进行体内交感神经记录，以测试 PVN 食欲素信号对交感传出的影响。实时 PCR 用于评估中枢给予食欲素 A 对 SD 大鼠 PVN PICs 表达的影响。为了测试食欲素 A 诱导的 PICs 增加是否仅通过食欲素受体 1（OX1R）介导，用不同剂量的食欲素 A 孵育表达 OX1R 的 PC12（PC12-OX1R）细胞，然后测量 PICs mRNA 和免疫反应性。
将食欲素 A（25 pmol）微注射到 PVN 中可显著增加 SD 大鼠的内脏 SNA（93.5%）和肾 SNA（83.3%），而 OX1R 拮抗剂 SB408124 可减弱这些增加。向 SD 大鼠侧脑室注射食欲素 A（0.2 nmol）可增加 PVN 中 PICs 的 mRNA 水平，包括 IL-1-β（2.7 倍）、IL-6（1.7 倍）和 TNF-α（1.5 倍），以及 Fra1（1.6 倍）。食欲素 A 处理 PC12-OX1R 细胞可导致 PICs 和 Fra1（AP1 转录因子的一个亚基）的表达呈剂量和时间依赖性增加。AP1 阻断剂姜黄素阻断了 PICs 的增加。
室旁核食欲素系统的激活参与了 SNA 的调节，可能是通过触发 AP1-PICs 途径。
