Department of Intensive Care, Raymond Poincaré Hospital, Garches, France.
PLoS One. 2011;6(11):e25905. doi: 10.1371/journal.pone.0025905. Epub 2011 Nov 3.
The mechanisms of septic shock-associated adrenal insufficiency remain unclear. This study aimed at investigating the synthesis of corticotropin-releasing hormone (CRH) and vasopressin (AVP) by parvocellular neurons and the antehypophyseal expression of ACTH in human septic shock and in an experimental model of sepsis.
To test the hypothesis that ACTH secretion is decreased secondarily to alteration of CRH or AVP synthesis, we undertook a neuropathological study of the antehypophyseal system in patients who had died from septic shock and rats with experimental faecal peritonitis.
Brains obtained in 9 septic shock patients were compared to 10 nonseptic patients (controls). Parvocellular expression of AVP and CRH mRNA were evaluated by in situ hybridization. Antehypophyseal expression of ACTH, vasopressin V1b and CRH R1 receptors and parvocellular expression of iNOS in the PVN were evaluated by immunohistochemistry. The same experiments were carried out in a fecal peritonitis-induced model of sepsis. Data from septic rats with (n = 6) or without (n = 10) early death were compared to sham-operated (n = 8) animals.
In patients and rats, septic shock was associated with a decreased expression of ACTH, unchanged expression of V1B receptor, CRHR1 and AVP mRNA, and increased expression of parvocellular iNOS compared to controls. Septic shock was also characterized by an increased expression of CRH mRNA in rats but not in patients, who notably had a greater duration of septic shock.
The present study suggests that in humans and in rats, septic shock is associated with decreased ACTH synthesis that is not compensated by its two natural secretagogues, AVP and CRH. One underlying mechanism might be increased expression of iNOS in hypothalamic parvocellular neurons.
脓毒性休克相关肾上腺功能不全的机制仍不清楚。本研究旨在研究促肾上腺皮质激素释放激素（CRH）和血管加压素（AVP）的合成以及 ACTH 在人类脓毒性休克和脓毒症实验模型中的前垂体表达。
为了检验 ACTH 分泌减少是继发于 CRH 或 AVP 合成改变的假设，我们对死于脓毒性休克的患者和患有实验性粪便性腹膜炎的大鼠的前垂体系统进行了神经病理学研究。
将 9 例脓毒性休克患者的大脑与 10 例非脓毒性患者（对照组）进行比较。通过原位杂交评估 AVP 和 CRH mRNA 的小细胞表达。通过免疫组织化学评估 ACTH、血管加压素 V1b 和 CRH R1 受体在前垂体中的表达以及 PVN 中小细胞 iNOS 的表达。在粪便性腹膜炎诱导的脓毒症模型中进行了相同的实验。将伴有（n = 6）或不伴有（n = 10）早期死亡的脓毒性大鼠的数据与假手术（n = 8）动物进行了比较。
在患者和大鼠中，与对照组相比，脓毒性休克与 ACTH 表达减少、V1B 受体、CRHR1 和 AVP mRNA 表达不变以及小细胞 iNOS 表达增加相关。脓毒性休克还伴有大鼠中 CRH mRNA 表达增加，但在患者中未见增加，患者的脓毒性休克持续时间明显更长。
本研究表明，在人类和大鼠中，脓毒性休克与 ACTH 合成减少有关，其两个天然促分泌素 AVP 和 CRH 不能代偿。一个潜在的机制可能是下丘脑小细胞神经元中 iNOS 表达增加。
