Gaykema R P, Dijkstra I, Tilders F J
Research Institute for Neurosciences, Vrije Universiteit, Department of Pharmacology, Amsterdam, The Netherlands.
Endocrinology. 1995 Oct;136(10):4717-20. doi: 10.1210/endo.136.10.7664696.
In order to assess the possibility that endotoxin-induced activation of the hypothalamus-pituitary-adrenal (HPA) axis is mediated by vagal afferents, we studied the effects of transection of the vagal nerves on endotoxin-induced Fos expression in hypothalamic corticotropin-releasing hormone (CRH) neurons and plasma ACTH and corticosterone responses. Groups of rats were subjected to sham surgery, complete subdiaphragmatic vagotomy (SVGX), or selective transection of the hepatic branch (HVGX). Two weeks after surgery, endotoxin or saline was injected i.p. and rats were sacrificed by decapitation two hours later. SVGX blocked or attenuated the ACTH response to 20 and 250 micrograms/kg endotoxin, respectively. HVGX did not suppress the ACTH response to either endotoxin dose. In addition, corticosterone responses were not affected by SVGX or HVGX. The endotoxin-induced Fos expression in CRH neurons was suppressed in SVGX, but not in HVGX animals. These observations lead us to postulate that the CRH and ACTH responses to a low dose of endotoxin are mediated by vagal afferents. The responses to a high dose of endotoxin involve additional neuronal or humoral pathways.
为了评估内毒素诱导的下丘脑 - 垂体 - 肾上腺（HPA）轴激活是否由迷走神经传入介导，我们研究了迷走神经切断术对内毒素诱导的下丘脑促肾上腺皮质激素释放激素（CRH）神经元中Fos表达以及血浆促肾上腺皮质激素（ACTH）和皮质酮反应的影响。将大鼠分组进行假手术、完全膈下迷走神经切断术（SVGX）或肝支选择性切断术（HVGX）。术后两周，腹腔注射内毒素或生理盐水，两小时后断头处死大鼠。SVGX分别阻断或减弱了对20和250微克/千克内毒素的ACTH反应。HVGX并未抑制对任何一种内毒素剂量的ACTH反应。此外，皮质酮反应不受SVGX或HVGX影响。内毒素诱导的CRH神经元中Fos表达在SVGX大鼠中受到抑制，但在HVGX大鼠中未受抑制。这些观察结果使我们推测，对低剂量内毒素的CRH和ACTH反应由迷走神经传入介导。对高剂量内毒素的反应涉及其他神经或体液途径。
