Chikada N, Imaki T, Harada S, Nakajima K, Naruse M, Yoshimoto T, Seki T, Tanabe A, Takano K
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan.
Endocr J. 2000 Jun;47(3):221-9. doi: 10.1507/endocrj.47.221.
The hypothalamo-pituitary-adrenal (HPA) axis activity of Lewis rats has been reported to be hyporesponsive to immune challenge, and nitric oxide (NO) has been demonstrated to be involved in the regulation of the HPA axis during the response to immune challenge. The present study investigates the effect of systemic injection of lipopolysaccharide (LPS) on NO production within the paraventricular nucleus (PVN) of immature female Fisher-344 (F344) and Lew/N rats (Lew/N), to clarify the pathophysiological role of NO in the dysregulation of the HPA axis in Lewis/N. Intraperitoneal injection of 25 mg/kg LPS significantly increased neuronal NO synthase (nNOS) mRNA expression in the PVN of F344 rats, but did not change nNOS mRNA levels in the PVN of Lew/N rats. CRF mRNA levels in the PVN significantly increased in response to LPS injection only in F344 rats. In contrast, inducible NOS (iNOS) mRNA increased similarly in both strains. These results demonstrated a defect of up-regulation of nNOS gene expression in the PVN of Lew/N rats following immune challenge. The defect appears to be associated with the dysfunction of the HPA axis in this strain. An increase in iNOS mRNA may partially restore NO production in the PVN.
据报道，Lewis大鼠的下丘脑 - 垂体 - 肾上腺（HPA）轴活性对免疫挑战反应低下，并且一氧化氮（NO）已被证明在免疫挑战反应期间参与HPA轴的调节。本研究调查了全身注射脂多糖（LPS）对未成熟雌性Fisher - 344（F344）和Lew / N大鼠（Lew / N）室旁核（PVN）内NO产生的影响，以阐明NO在Lewis / N大鼠HPA轴失调中的病理生理作用。腹腔注射25 mg / kg LPS显著增加了F344大鼠PVN中神经元型一氧化氮合酶（nNOS）mRNA的表达，但未改变Lew / N大鼠PVN中nNOS mRNA的水平。仅在F344大鼠中，LPS注射后PVN中的促肾上腺皮质激素释放因子（CRF）mRNA水平显著增加。相反，诱导型一氧化氮合酶（iNOS）mRNA在两种品系中同样增加。这些结果表明，免疫挑战后Lew / N大鼠PVN中nNOS基因表达上调存在缺陷。该缺陷似乎与该品系中HPA轴的功能障碍有关。iNOS mRNA的增加可能部分恢复PVN中的NO产生。
