小柯机器人

近日，比利时根特大学Claude Libert及其小组发现，糖皮质激素抵抗和高乳酸血症共同导致了脓毒症的致命性休克。相关论文于2021年7月23日发表在《细胞—代谢》杂志上。

研究人员表明，糖皮质激素受体信号通路的缺陷通过降低乳酸清除率和使小鼠对乳酸诱导的毒性敏感而加剧了脓毒症的病理。后者是通过不受控制的血管内皮生长因子产生而施加的，导致血管渗漏和崩溃，出现严重的低血压、器官损伤和死亡，这些都是致命性脓毒症的典型特征。总之，脓毒症导致糖皮质激素受体失效和高乳酸血症，这共同导致了致命的血管崩溃。

据悉，脓毒症是一种潜在的致命性综合征，由对感染的不适应反应导致。感染后，糖皮质激素的产生是容忍脓毒症的一种补偿反应。然而，由于在糖皮质激素受体水平上迅速诱发的糖皮质激素抵抗，这种耐受性在脓毒症中被缓解。

附：英文原文

Title: Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis

Author: Jolien Vandewalle, Steven Timmermans, Ville Paakinaho, Lies Vancraeynest, Liza Dewyse, Tineke Vanderhaeghen, Charlotte Wallaeys, Lise Van Wyngene, Kelly Van Looveren, Louise Nuyttens, Melanie Eggermont, Sylviane Dewaele, Tiago R. Velho, Luis F. Moita, Sebastian Weis, Christoph Sponholz, Leo A. van Grunsven, Mieke Dewerchin, Peter Carmeliet, Karolien De Bosscher, Johan Van de Voorde, Jorma J. Palvimo, Claude Libert

Issue&Volume: 2021-07-23

Abstract: Sepsis is a potentially lethal syndrome resulting from a maladaptive response to infection.Upon infection, glucocorticoids are produced as a part of the compensatory responseto tolerate sepsis. This tolerance is, however, mitigated in sepsis due to a quicklyinduced glucocorticoid resistance at the level of the glucocorticoid receptor. Here,we show that defects in the glucocorticoid receptor signaling pathway aggravate sepsispathophysiology by lowering lactate clearance and sensitizing mice to lactate-inducedtoxicity. The latter is exerted via an uncontrolled production of vascular endothelialgrowth factor, resulting in vascular leakage and collapse with severe hypotension,organ damage, and death, all being typical features of a lethal form of sepsis. Inconclusion, sepsis leads to glucocorticoid receptor failure and hyperlactatemia, whichcollectively leads to a lethal vascular collapse.

DOI: 10.1016/j.cmet.2021.07.002

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00318-1

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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