Giuffre K A, Udelsman R, Listwak S, Chrousos G P
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Endocrinology. 1988 Jan;122(1):306-10. doi: 10.1210/endo-122-1-306.
Specific in vivo neutralization was used in an attempt to explore the roles of corticotropin-releasing hormone (CRH), ACTH, and beta-endorphin during surgical stress in Sprague-Dawley rats. Rats were randomly assigned to groups (n = 20-30/group) that received iv injections of rabbit antirat/human CRH (anti-r/hCRH), antihuman ACTH (anti-hACTH), antihuman beta-endorphin (anti-h beta-endorphin), or normal rabbit serum. Three hours later all animals were subjected to a uniform stress consisting of ether anesthesia, surgical laparotomy, and phlebotomy of 7 ml via the inferior vena cava. Survival rates were recorded, and RIAs were performed for ACTH, beta-endorphin, and corticosterone. Rats treated with anti-h beta-endorphin had a survival rate of 64%, which was significantly higher than that of the control group (33%; P less than 0.025, by analysis of variance). Anti-r/hCRH or anti-hACTH treatment was not associated with a change in survival rate. Plasma immunoreactive beta-endorphin levels were markedly decreased in the group treated with anti-h beta-endorphin (P less than 0.0001). Anti-r/hCRH had no effect on plasma immunoreactive ACTH or beta-endorphin. Plasma immunoreactive ACTH and corticosterone levels were decreased in the group treated with anti-hACTH (P less than 0.0001 and P less than 0.01, respectively). We conclude that 1) beta-endorphin immune neutralization is associated with a survival advantage during severe surgical stress, suggesting that circulating beta-endorphin might have deleterious effects during stress; 2) In severe stress, acute immune neutralization of CRH is not sufficient to inhibit ACTH, beta-endorphin, and corticosterone secretion, suggesting significant involvement of other secretagogues of the pituitary-adrenal axis; and 3) moderate decreases in corticosterone cannot affect survival, presumably because glucocorticoids play only a permissive role in maintaining cardiovascular stability during surgical stress.
采用特异性体内中和法，试图探讨促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）和β-内啡肽在Sprague-Dawley大鼠手术应激过程中的作用。将大鼠随机分为几组（每组n = 20 - 30只），分别静脉注射兔抗大鼠/人CRH（抗r/hCRH）、抗人ACTH（抗hACTH）、抗人β-内啡肽（抗hβ-内啡肽）或正常兔血清。3小时后，所有动物均接受由乙醚麻醉、剖腹手术及经下腔静脉放血7 ml组成的统一应激处理。记录存活率，并对ACTH、β-内啡肽和皮质酮进行放射免疫分析。用抗hβ-内啡肽处理的大鼠存活率为64%，显著高于对照组（33%；方差分析，P < 0.025）。抗r/hCRH或抗hACTH处理与存活率变化无关。抗hβ-内啡肽处理组血浆免疫反应性β-内啡肽水平明显降低（P < 0.0001）。抗r/hCRH对血浆免疫反应性ACTH或β-内啡肽无影响。抗hACTH处理组血浆免疫反应性ACTH和皮质酮水平降低（分别为P < 0.0001和P < 0.01）。我们得出结论：1）β-内啡肽免疫中和与严重手术应激期间的生存优势相关，提示循环β-内啡肽在应激期间可能具有有害作用；2）在严重应激时，CRH的急性免疫中和不足以抑制ACTH、β-内啡肽和皮质酮的分泌，提示垂体-肾上腺轴的其他促分泌素起重要作用；3）皮质酮适度降低不会影响生存，推测是因为糖皮质激素在手术应激期间维持心血管稳定性方面仅起允许作用。
