Orexin A increases sympathetic nerve activity through promoting expression of proinflammatory cytokines in Sprague Dawley rats.
Orexin A increases sympathetic nerve activity through promoting expression of proinflammatory cytokines in Sprague Dawley rats.
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DOI：
10.1111/apha.12963
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Shan Z
中科院分区：
文献类型：
--
作者：
Fan Y;Jiang E;Hahka T;Chen QH;Yan J;Shan Z
越来越多的证据表明，食欲素信号参与血压和心血管功能的调节。然而，其内在机制尚不清楚。在这里，我们测试的假设，在室旁核（PVN）的食欲素A信号上调增加交感神经活动（SNA）通过刺激促炎细胞因子（PIC）的表达。进行体内交感神经记录以测试PVN食欲素信号传导对Sprague道利（SD）大鼠交感神经流出的影响。采用实时荧光定量PCR技术检测中枢给予食欲素A对大鼠室旁核PICs表达的影响。为了测试食欲素A诱导的PIC增加是否仅由食欲素受体1（OX 1 R）介导，将表达OX 1 R的PC 12（PC 12-OX 1 R）细胞与不同剂量的食欲素A孵育，然后测量PIC mRNA和免疫反应性。PVN微量注射Orexin A（25 pmol）可显著增加SD大鼠内脏SNA（93.5%）和肾脏SNA（83.3%），OX 1 R拮抗剂SB 408124可减弱上述增加。侧脑室注射orexin A（0.2 nmol）可使PVN中的PICs（IL-1-β、IL-6、TNF-α）和Fra 1的mRNA水平增加2.7倍、1.7倍和1.5倍。Orexin A处理PC 12-OX 1 R细胞导致PIC和Fra 1（AP 1转录因子的亚基）表达的剂量和时间依赖性增加。PICs的增加被AP 1阻断剂姜黄素阻断。室旁核食欲素系统的激活可能通过激活AP 1-PICs通路参与SNA的调节。
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.
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发表时间：
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影响因子：
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影响因子：
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