Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan, ROC.
Arch Toxicol. 2012 Mar;86(3):453-63. doi: 10.1007/s00204-011-0761-7. Epub 2011 Oct 12.
It has been reported that oxidative stress, antioxidants, and neuropeptide Y (NPY) are involved in regulating the feeding behavior of phenylpropanolamine (PPA), a sympathomimetic drug. This study explored whether transcription factor NF-κB is involved in this effect. Rats were treated daily with PPA for 4 days. Changes in hypothalamic NF-κB, NPY, superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels during PPA treatment were assessed and compared. Results showed that NF-κB, SOD, and GPx increased, with a maximal response on Day 2, while the food intake and NPY decreased with the biggest reduction on Day 2 during PPA treatment. To further determine whether NF-κB was involved, intracerebroventricular infusion of antisense oligonucleotide was performed at 1 h before daily PPA in free-moving rats. Cerebral NF-κB knockdown could modify PPA anorexia and the expressions of NPY, SOD, and GPx. It is suggested that hypothalamic NF-κB participates in the reciprocal regulation of NPY and antioxidants, which mediated the appetite-suppressing effect of PPA. Results may further the understanding of the molecular mechanisms of PPA.
据报道，氧化应激、抗氧化剂和神经肽 Y（NPY）参与调节苯丙醇胺（PPA）的摄食行为，PPA 是一种拟交感胺药物。本研究探讨了转录因子 NF-κB 是否参与这种作用。大鼠每天用 PPA 处理 4 天。评估并比较了 PPA 处理过程中下丘脑 NF-κB、NPY、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）水平的变化。结果表明，NF-κB、SOD 和 GPx 增加，最大反应发生在第 2 天，而摄食量和 NPY 减少，最大减少发生在第 2 天。为了进一步确定 NF-κB 是否参与其中，在自由活动大鼠每日 PPA 前 1 小时进行脑室输注反义寡核苷酸。大脑 NF-κB 敲低可以改变 PPA 引起的厌食症以及 NPY、SOD 和 GPx 的表达。提示下丘脑 NF-κB 参与 NPY 和抗氧化剂的相互调节，介导 PPA 的食欲抑制作用。研究结果可能进一步了解 PPA 的分子机制。
