IL-6 signaling pathway contributes to exercise pressor reflex in rats with femoral artery occlusion in association with Kv4 activity in muscle afferent nerves.
IL-6 signaling pathway contributes to exercise pressor reflex in rats with femoral artery occlusion in association with Kv4 activity in muscle afferent nerves.
复制标题
DOI：
10.14814/phy2.14935
复制
发表时间：
2021-07
影响因子：
2.5
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Li Q;Qin L;Li J
白细胞介素-6（IL-6）通过反式信号通路对股动脉结扎大鼠肌肉感觉神经增强的运动加压反射起调节作用，但其机制尚不清楚。已知电压门控钾通道亚家族成员Kv 4通道有助于感觉神经元的兴奋性和神经元信号转导。因此，在本研究中，我们确定了1）IL-6调节股动脉结扎诱导的外周动脉疾病（PAD）大鼠的过度运动升压反射，2）肌肉背根神经节（DRG）神经元中的Kv 4通道参与了IL-6反式信号通路的作用。我们发现股动脉闭塞3天的PAD大鼠DRG中IL-6及其受体IL-6 R的蛋白水平增加。通过动脉内给予PAD大鼠后肢肌肉中的SC 144（一种gp 130抑制剂），抑制肌肉传入的IL-6反式信号通路（gp 130），缓解了对静态肌肉收缩的血压反应。另一方面，我们发现3天的股动脉闭塞降低了大鼠肌肉DRG神经元中Kv 4电流的幅度。人IL-6/IL-6 R α融合蛋白（H. IL-6/6 R α），而不是单独的IL-6显著抑制肌DRG神经元的Kv 4电流; H. IL-6/6 R α在很大程度上被SC 144逆转。总之，我们的数据表明，通过反式信号通路上调缺血后肢肌肉传入神经中的IL-6抑制Kv 4通道的活性，从而可能导致PAD中运动升压反射的调整。白细胞介素-6（IL-6）调节股动脉结扎诱导的外周动脉疾病（PAD）大鼠的过度运动升压反射。肌肉背根神经节（DRG）神经元中的Kv 4通道参与IL-6反式信号通路所发挥的作用。
Interleukin‐6 (IL‐6) via trans‐signaling pathway plays a role in modifying muscle sensory nerve‐exaggerated exercise pressor reflex in rats with ligated femoral arteries, but the underlying mechanisms are poorly understood. It is known that voltage‐gated potassium channel subfamily member Kv4 channels contribute to the excitabilities of sensory neurons and neuronal signaling transduction. Thus, in this study, we determined that 1) IL‐6 regulates the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD) induced by femoral artery ligation and 2) Kv4 channels in muscle dorsal root ganglion (DRG) neurons are engaged in the role played by IL‐6 trans‐signaling pathway. We found that the protein levels of IL‐6 and its receptor IL‐6R expression were increased in the DRGs of PAD rats with 3‐day of femoral artery occlusion. Inhibition of muscle afferents’ IL‐6 trans‐signaling pathway (gp130) by intra‐arterial administration of SC144, a gp130 inhibitor, into the hindlimb muscles of PAD rats alleviated blood pressure response to static muscle contraction. On the other hand, we found that 3‐day femoral occlusion decreased amplitude of Kv4 currents in rat muscle DRG neurons. The homo IL‐6/IL‐6Rα fusion protein (H. IL‐6/6Rα), but not IL‐6 alone significantly inhibited Kv4 currents in muscle DRG neurons; and the effect of H. IL‐6/6Rα was largely reverted by SC144. In conclusion, our data suggest that via trans‐signaling pathway upregulated IL‐6 in muscle afferent nerves by ischemic hindlimb muscles inhibits the activity of Kv4 channels and thus likely leads to adjustments of the exercise pressor reflex in PAD. Interleukin‐6 (IL‐6) regulates the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD) induced by femoral artery ligation. Kv4 channels in muscle dorsal root ganglion (DRG) neurons are engaged in the role played by IL‐6 trans‐signaling pathway.