Department of Pathology, University of California-Irvine Sch. of Med., Irvine, CA 92625. United States.
Curr Pharm Des. 2017;23(27):4029-4041. doi: 10.2174/1381612823666170622110046.
The first scientific publication on 'general adaption syndrome', or as we know today 'biologic stress' has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/ stressors, but his idea about a 'nonspecific bodily response' originated from his observations of sick patients whom he had seen as a medical student and young clinician. Autopsy of stressed rats revealed three major, grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as well as hemorrhagic gastric erosions/ulcers (the "stress triad"). Based on this and additional observations, he concluded that the key master organ in stress reactions is the adrenal cortex (although he also accepted the limited and short lasting effect of catecholamines released from the adrenal medulla) which stimulated by an increased secretion of ACTH, secreted by the anterior pituitary gland. He thus identified the first molecular mediators of the stress reaction, i.e., steroids released from the adrenal cortex that we call today glucocorticoids, based on his classification and naming of steroids. At the end of a very productive life in experimental medicine, Selye recognized that under both unpleasant and demanding stressors as well as positive, rewarding stimuli adrenal cortex releases the same glucocorticoids and only certain brain structures may distinguish the stimuli under distress and eustress - terms he introduced in 1974, that also contained his last definition of stress: the nonspecific response of the body on any demand on it. After brief description of the history of stress research, the rest of this review is focused on one element of stress triad, i.e., gastroduodenal ulceration, especially its pathogenesis, prevention and treatment. Following a short description of acute gastroprotection, discovered by one of Selye's students, we discuss new molecular mediators of gastroduodenal ulceration like dopamine and new drugs that either only heal (very potently, on molar basis) or prevent and heal ulcers like sucralfate derivatives and the relatively new peptide BPC-157. We conclude that despite the extensive and multidisciplinary research on stress during the last 80 years, a lot of basic and clinical research is needed to better understand the manifestations, central and peripheral molecular regulators of stress response, especially the modes of prevention/management of distress or its transformation into eustress and the treatment of stress-related diseases.
1936 年，年仅 29 岁的汉斯·塞利（Hans Selye）在《自然》杂志上发表了第一篇关于“一般适应综合征”（即我们今天所知的“生物应激”）的科学论文。他在这篇简短的论文中没有引用或说明，其结果基于对暴露于严重刺激/应激源的大鼠的实验，但他关于“非特异性身体反应”的想法源于他对作为医学生和年轻临床医生所看到的患病患者的观察。应激大鼠的尸检显示出三大明显的肉眼可见变化：肾上腺充血和肿大、胸腺和淋巴结萎缩以及胃出血性溃疡（“应激三联征”）。基于此以及其他观察结果，他得出结论，应激反应的关键主要器官是肾上腺皮质（尽管他也接受了来自肾上腺髓质释放的儿茶酚胺的有限且短暂的作用），它被垂体前叶分泌的促肾上腺皮质激素（ACTH）刺激。因此，他根据自己对类固醇的分类和命名，确定了应激反应的第一批分子介质，即肾上腺皮质释放的类固醇，我们今天称之为糖皮质激素。在实验医学的非常富有成效的一生中，塞利意识到，在不愉快和要求苛刻的应激源以及积极的、有益的刺激下，肾上腺皮质都会释放相同的糖皮质激素，只有某些大脑结构才能区分应激和正应激下的刺激——这些术语是他在 1974 年提出的，其中还包含他对压力的最后定义：身体对任何需求的非特异性反应。简要介绍应激研究的历史后，本综述的其余部分将重点介绍应激三联征的一个元素，即胃十二指肠溃疡，特别是其发病机制、预防和治疗。在简要描述塞利的一位学生发现的急性胃保护作用后，我们讨论了胃十二指肠溃疡的新分子介质，如多巴胺和新的药物，这些药物要么仅能强力（按摩尔基础计算）治愈，要么预防和治愈溃疡，如蔗糖硫酸酯衍生物和相对较新的肽 BPC-157。我们得出的结论是，尽管在过去的 80 年里对压力进行了广泛的多学科研究，但仍需要进行大量的基础和临床研究，以更好地了解压力反应的表现、中枢和外周分子调节剂，特别是应激的预防/管理模式或其向正应激的转变，以及应激相关疾病的治疗。
