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脓毒症是由致病微生物感染引发的全身炎症反应综合征(SIRS),合并血压降低且经快速液体复苏后血压仍不能恢复正常者
称为脓毒性休克(Septic shock),其中一部分患者发展为多器官功能障碍综合症(MODS)。脓毒症病死率居高不下。每10 万人口中
约50-300 人会发生严重脓毒症,其短期死亡率达20%-25%,当发展为脓毒性休克时其死亡率达50%。整合消灭致病微生物、阻断
炎症介质和处理MODS等措施的" 集束化"治疗并未显著降低脓毒症患者的病死率。糖皮质激素具有强大的抗炎作用,但诸多
的临床研究对糖皮质激素疗效的评价褒贬不一,糖皮质激素是否有利于脓毒症的转归一直饱受争议[3]。本文仅就糖皮质激素在
严重脓毒症及脓毒性休克中的治疗进展综述如下,并希望能进一步探讨发生严重脓毒症及脓毒性休克时,机体对糖皮质激素反
应复杂性的原因,以及在以后的研究中对相对肾上腺皮质功能不全的诊断标准及对糖皮质激素用药和停药时机的选择更加明确。 相似文献
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Sepsis is a complex pathophysiological disorder arising from a systemic inflammatory response to infection. Patients are clinically classified according to the presence of signs of inflammation alone, multiple organ failure (MOF), or organ failure plus hypotension (septic shock). The organ damage that occurs in MOF is not a direct effect of the pathogen itself, but rather of the dysregulated inflammatory response of the patient. Although mechanisms underlying MOF are not completely understood, a disruption in cellular energetic metabolism is increasingly implicated. In this review, we describe how various factors affecting cellular ATP supply and demand appear to be altered in sepsis, and how these vary through the timecourse. We will emphasise the need for an integrated systems approach to determine the relative importance of these factors in both the failure and recovery of different organs. A modular framework is proposed that can be used to assess the control hierarchy of cellular energetics in this complex pathophysiological condition. 相似文献
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脓毒症是由致病微生物感染引发的全身炎症反应综合征(SIRS),合并血压降低且经快速液体复苏后血压仍不能恢复正常者称为脓毒性休克(Septic shock),其中一部分患者发展为多器官功能障碍综合症(MODS)。由于目前临床上仍缺乏早期敏感性诊断手段,脓毒症病死率居高不下。每10万人口中约50-300人会发生严重脓毒症,其短期死亡率达20%-25%,当发展为脓毒性休克时其死亡率达50%。随着分子生物学和现代生物技术的不断发展,人们发现多种生物标志物在脓毒症的早期诊断、病情及预后判断,疗效评估中发挥重要作用。因此深入了解脓毒症病理生理机制中不同生物标志物的意义及价值,对于脓毒症及其并发症的早期识别及干预,降低患者病死率及改善患者生活质量有积极意义。本文综述了近几年来对脓毒症的诊断和预后有一定价值的主要标志物及其应用。 相似文献
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Murray MJ 《The Yale journal of biology and medicine》1998,71(6):485-491
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脓毒症是由感染引起的全身炎症反应综合征,证实有感染灶存在或有高度可疑的感染灶。脓毒症是ICU内重症患者的主要死亡原因,且发病率随着年龄的增长而逐渐增加。近十年来,虽然政府在救治脓毒症患者中投入了巨大的资金和技术支持,但源于脓毒症或脓毒性休克患者的病死率仍高达30%~60%。心血管系统在脓毒症与脓毒性休克的病理生理学中扮演着重要着色。过去的四五十年,开展了很多脓毒性心肌功能障碍方面的研究,也积累了不少循证医学证据。然而,心脏只是心血管系统的一部分。诸如脓毒症患者机体血流动力学的变化系脓毒症对心脏的直接效应,还是脓毒症引起心脏前、后负荷及神经体液因素的变化,继而引起心脏继发改变的研究,至今仍在继续。本文概述了近年来脓毒性心肌功能障碍的研究进展,使读者更全面地了解脓毒性心肌功能障碍的病理生理学改变,合理有效地指导脓毒症和脓毒性休克患者的临床救治。 相似文献
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《Cytokine》2016
Early recovery from shock improves prognosis in patients with severe sepsis and septic shock. During this period, cytokine imbalances mediate the development of organ damage and mortality. In Japan, we have access to hemoperfusion using an immobilized polymyxin B fiber column for endotoxin removal (PMX-DHP) and continuous hemodiafiltration (CHDF) as artificial support for patients with septic shock, with the aim of improving hemodynamics and organ dysfunction caused by elevated inflammatory cytokines and mediators. In this Short communication, we discuss recent findings showing anti-inflammatory treatment following these continuous renal replacement therapies in sepsis. 相似文献
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Sepsis: current concepts in intracellular signaling 总被引:1,自引:0,他引:1
Strassheim D Park JS Abraham E 《The international journal of biochemistry & cell biology》2002,34(12):762-1533
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Cheyuo C Jacob A Wang P 《American journal of physiology. Endocrinology and metabolism》2012,302(3):E265-E272
Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. 相似文献
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Toll-like receptors, new horizons in sepsis 总被引:1,自引:0,他引:1
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Patrícia O. Benedet Angela C.O. Menegatti Muryel C. Gonçalves Hernán Terenzi Jamil Assreuy 《生物化学与生物物理学报:疾病的分子基础》2018,1864(1):307-316
Cardiovascular dysfunction and organ damage are hallmarks of sepsis and septic shock. Protein S-nitrosylation by nitric oxide has been described as an important modifier of protein function. We studied whether protein nitrosylation/denitrosylation would impact positively in hemodynamic parameters of septic rats. Polymicrobial sepsis was induced by cecal ligation and puncture. Female Wistar rats were treated with increasing doses of DTNB [5,5′-dithio-bis-(2-nitrobenzoic acid)] 30 min before or 4 or 12 h after sepsis induction. Twenty-four hours after surgery the following data was obtained: aorta response to phenylephrine, mean arterial pressure, vascular reactivity to phenylephrine, biochemical markers of organ damage, survival and aorta protein nitrosylation profile. Sepsis substantially decreases blood pressure and the response of aorta rings and of blood pressure to phenylephrine, as well as increased plasma levels of organ damage markers, mortality of 60% and S-nitrosylation of aorta proteins increased during sepsis. Treatment with DTNB 12 h after septic shock induction reversed the loss of response of aorta rings and blood pressure to vasoconstrictors, reduced organ damage and protein nitrosylation and increased survival to 80%. Increases in protein S-nitrosylation are related to cardiovascular dysfunction and multiple organ injury during sepsis. Treatment of rats with DTNB reduced the excessive protein S-nitrosylation, including that in calcium-dependent potassium channels (BKCa), reversed the cardiovascular dysfunction, improved markers of organ dysfunction and glycemic profile and substantially reduced mortality. Since all these beneficial consequences were attained even if DTNB was administered after septic shock onset, protein (de)nitrosylation may be a suitable target for sepsis treatment. 相似文献
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Paula Giselle Czaikoski José Maurício Segundo Correia Mota Daniele Carvalho Nascimento Fabiane S?nego Fernanda Vargas e Silva Castanheira Paulo Henrique Melo Gabriela Trentin Scortegagna Rangel Leal Silva Romualdo Barroso-Sousa Fabrício Oliveira Souto Antonio Pazin-Filho Florencio Figueiredo José Carlos Alves-Filho Fernando Queiróz Cunha 《PloS one》2016,11(2)
Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are relevant actors in the pathogenesis of sepsis. 相似文献
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Toll receptors,CD14, and macrophage activation and deactivation by LPS 总被引:17,自引:0,他引:17
This review will focus on the molecular mechanisms of macrophage activation and desensitization by bacterial lipopolysaccharide (LPS). The most recent advances in the understanding of the function of the LPS receptor complex and its role in the development of the septic shock syndrome and endotoxin tolerance will be discussed. 相似文献
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Doerschug KC Delsing AS Schmidt GA Haynes WG 《American journal of physiology. Heart and circulatory physiology》2007,293(2):H1065-H1071
Severe sepsis is a systemic inflammatory response to infection resulting in acute organ dysfunction. Vascular perfusion abnormalities are implicated in the pathology of organ failure, but studies of microvascular function in human sepsis are limited. We hypothesized that impaired microvascular responses to reactive hyperemia lead to impaired oxygen delivery relative to the needs of tissue and that these impairments would be associated with organ failure in sepsis. We studied 24 severe sepsis subjects 24 h after recognition of organ dysfunction; 15 healthy subjects served as controls. Near-infrared spectroscopy (NIRS) was used to measure tissue 1) microvascular hemoglobin signal strength and 2) oxygen saturation of microvascular hemoglobin (StO2). Both values were measured in thenar skeletal muscle before and after 5 min of forearm stagnant ischemia. At baseline, skeletal muscle microvascular hemoglobin was lower in septic than control subjects. Microvascular hemoglobin increased during reactive hyperemia in both groups, but less so in sepsis. StO2 at baseline and throughout ischemia was similar between the two groups; however, the rate of tissue oxygen consumption was significantly slower in septic subjects than in controls. The rate of increase in StO2 during reactive hyperemia was significantly slower in septic subjects than in controls; this impairment was accentuated in those with more organ failure. We conclude that organ dysfunction in severe sepsis is associated with dysregulation of microvascular oxygen balance. NIRS measurements of skeletal muscle microvascular perfusion and reactivity may provide important information about sepsis and serve as endpoints in future therapeutic interventions aimed at improving the microcirculation. 相似文献
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Sameer H. Fatani Abeer Ahmed ALrefai Hiba S. AL-Amodi Hala F. Kamel Kasem AL-Khatieb Hamdy Bader 《Molecular biology reports》2018,45(5):839-847
Critically ill patients revealed significant adverse outcomes (sepsis, septic shock, organ dysfunction/failure, and mortality) despite variable effort. Aim: this study evaluated the association of TNF-a?238 (rs 361525) with adverse outcomes in critically ill patients. TNF-α?238 (rs 361525) SNP was performed by RT-PCR on 200 critically-ill patients (112 had severe sepsis and septic shock and 88 were septic), 127 of them had AKI. Urinary N-acetyl-β-(d)-glucosaminidase and serum creatinine were assessed by modified Jaffé and ELISA respectively. These results revealed that heterozygous genotype GA of TNF-α?238 (rs 361525) SNP significantly increased the risk of adverse-outcome (mortality rate) (P?=?0.0001; OR 8.9), regardless of organ dysfunction (P?=?0.09) or severity of sepsis (P?=?0.6). Moreover, heterozygous genotype GA of TNF-α?238 (rs 361525) SNP was significantly associated with inflammatory marker (sTNF-α) (P?=?0.014) and tubular injury marker (uNAG) (P?=?0.001) that displayed a significant association with severity of sepsis (0.001, 0.035) and organ dysfunction (0.012, 0.0001) respectively. In critically ill patients with sepsis induced AKI, serum TNF-α and uNAG measured at admission can predict severity of sepsis and AKI (defined by REFILE) occurrence along with pre-existing CKD and DM. However, TNF?238 yielded additional prognostic information on ICU mortality irrelevant to AKI in septic patients. 相似文献
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The central nervous system (CNS) is a major dose-limiting organ in clinical radiotherapy (XRT). The underlying mechanisms of radiation-induced injury in this organ remain unclear. For many years, research has focused on identifying the major target cells of damage, and depletion of target cells due to reproductive or clonogenic cell death was believed to be the primary cause of tissue damage and organ failure. There is now an increasing body of data indicating that the response of the CNS after XRT is a continuous and interacting process. This review addresses some of the recent advances in our understanding of the mechanisms of CNS radiation damage. Specifically, the focus is on apoptotic cell death, and cell death and injury mediated by secondary damage. These potentially reversible components of the injury response provide important targets for neuroprotective interventions. 相似文献
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Protection from septic shock by neutralization of macrophage migration inhibitory factor 总被引:36,自引:0,他引:36
Calandra T Echtenacher B Roy DL Pugin J Metz CN Hültner L Heumann D Männel D Bucala R Glauser MP 《Nature medicine》2000,6(2):164-170
Identification of new therapeutic targets for the management of septic shock remains imperative as all investigational therapies, including anti-tumor necrosis factor (TNF) and anti-interleukin (IL)-1 agents, have uniformly failed to lower the mortality of critically ill patients with severe sepsis. We report here that macrophage migration inhibitory factor (MIF) is a critical mediator of septic shock. High concentrations of MIF were detected in the peritoneal exudate fluid and in the systemic circulation of mice with bacterial peritonitis. Experiments performed in TNFalpha knockout mice allowed a direct evaluation of the part played by MIF in sepsis in the absence of this pivotal cytokine of inflammation. Anti-MIF antibody protected TNFalpha knockout from lethal peritonitis induced by cecal ligation and puncture (CLP), providing evidence of an intrinsic contribution of MIF to the pathogenesis of sepsis. Anti-MIF antibody also protected normal mice from lethal peritonitis induced by both CLP and Escherichia coli, even when treatment was started up to 8 hours after CLP. Conversely, co-injection of recombinant MIF and E. coli markedly increased the lethality of peritonitis. Finally, high concentrations of MIF were detected in the plasma of patients with severe sepsis or septic shock. These studies define a critical part for MIF in the pathogenesis of septic shock and identify a new target for therapeutic intervention. 相似文献
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