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世界华人消化杂志 1998年第S2期6卷 430-430页

作者：王志华张洪川石小彦河南省濮阳市中原油田井下职工医院 457061

目的探讨重组人生长激素（rhGH）对进行全胃肠外营养支持（TPN）的脓毒症患者代谢的影响．方法按照1991年美国ACCP／SCCM关于脓毒症的诊断标准选择肠瘘、肠破裂或重症急性胰腺炎并腹腔感染的脓毒症患者11例分为rhGH组和对照组．rhGH组7... 详细信息

目的探讨重组人生长激素（rhGH）对进行全胃肠外营养支持（TPN）的脓毒症患者代谢的影响．方法按照1991年美国ACCP／SCCM关于脓毒症的诊断标准选择肠瘘、肠破裂或重症急性胰腺炎并腹腔感染的脓毒症患者11例分为rhGH组和对照组．rhGH组7例，APACHEⅡ评分12．0±1．8分对照组4例APACHEⅡ评分11．6±2．1分．两组患者均在确诊后施行相应的肠造瘘，肠吻合或（和）腹腔引流术．在给予相应的抗生素治疗的同时，rhGH组应用TPN加rhGH治疗，对照组进行TPN治疗．两组患者的TPN方案完全相同，非蛋白热能为125．52KJ／（kg·d），葡萄糖和脂肪乳供能比为1：1，供氧量为0．25g／（kg·d）．前瞻性对比观察两组患者的氮平衡（NB），血浆蛋白，体重等代谢情况的变化实验观察进行7d．结果rhGH组3d后实现正NB，其累积NB值为8．76g±5．24g，实验前后NB变化非常显著（P＜0．01）对照组7d后仍为负NB，累积NB值为-1．03g±3．64g．两组患者的NB变化差异显著（P＜0．05）．实验前后，rhGH组的转铁蛋白和前清蛋白显著升高（P＜0．05），与对照组比较也差异显著（P＜0．05）．rhGH组体重丧失明显少于对照组（1．26kg±1．24kg／4．41kg±2．12kg）．但经统计学检验未显示出显著性．结论rhGH具有促进处于高分解代谢状态的脓毒症?

关键词：生长激素脓毒症/代谢胃肠外营养

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Metabolic response to severe surgical illness: Overview

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WORLD JOURNAL OF SURGERY 2000年第6期24卷 705-711页

作者： Wilmore, DW Harvard Univ Brigham & Womens Hosp Sch Med Dept Surg Boston MA 02115 USA

Severe surgical illness results in metabolic responses that mobilize substrate (amino acids and fatty acids) from body stores to support vital organs, enhance resistance to infection, and ensure wound healing. Central to this process is the redistribution of body protein, which moves From skeletal muscle to support the central viscera. If unsupported, this protein-wasting state could result in prolonged convalescence, diminished immunity, and poor wound healing. Present evidence suggests that the central nervous system plays a major role in regulating this protein catabolic response. Infusing exceedingly small quantities of the proinflammatory cytokines into the brain can mimic injury responses, and central cytokine blockade may be one therapeutic approach to attenuating these responses safely in the future. Additional evidence also demonstrates that the function of the hypothalamus and anterior pituitary is dampened during the later stages of severe surgical illness, and the possibility of hormonal replacement therapy needs to he explored.

关键词：身体成分中枢神经系统/生理学蛋白质类/代谢脓毒症/代谢应激生理学/代谢外科手术伤口愈合/生理学创伤和损伤/代谢人类

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Manipulations of the metabolic response for management of patients with severe surgical illness: Review

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WORLD JOURNAL OF SURGERY 2000年第6期24卷 696-704页

作者： Connolly, AB Vernon, DR Univ Auckland Dept Surg Auckland 1 New Zealand

The metabolic response to severe surgical illness is complex and varied. Much recent laboratory and clinical research has focused on increasing our understanding of the metabolic response and the development of new therapies designed to modify this response. Antiinflammatory agents can target harmful aspects of the metabolic response;the immune system can be stimulated;and anabolic factors can be used in an attempt to enhance recovery. The nutritional support of the surgical patient remains crucial, but the effects of new additives are being studied in a variety of surgical conditions. As yet, few of these "novel" agents have found an established role in the management of surgical patients. This review focuses on many "novel" agents or those that do not yet have a clearly defined role in surgical illness. Clinical trials in the areas of severe sepsis, major surgical trauma, and major elective surgery have been emphasized.

关键词：生长物质/代谢营养支持血小板活化因子/生理学脓毒症/代谢休克脓毒性/代谢应激生理学/代谢外科手术肿瘤坏死因子α/代谢创伤和损伤/代谢动物人类

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Overview of modern management of patients with critical injury and severe sepsis

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WORLD JOURNAL OF SURGERY 2000年第6期24卷 655-663页

作者： Streat, SJ Plank, LD Hill, GL Univ Auckland Auckland Hosp Dept Surg Auckland 1003 New Zealand Auckland Hosp Dept Crit Care Med Auckland 1003 New Zealand

Over the last 10 years there have been substantial changes in the issues confronting intensivists and surgeons caring for critically ill patients. A substantial increase in the number of elderly patients with surgical illness and complex co-morbidity has accompanied the increase in the proportion of elderly in populations in the developed world. This phenomenon has been seen particularly with sepsis, Incidence rates for blunt trauma have declined overall, but the problems of the elderly trauma patient have become more evident. Major elective surgery remains a common indication for short-term intensive care in many countries, but the need for cost-containment has led to increased use of high-dependency care for many such patients. Expectations of both society and clinicians have increased, and this has been reflected in the increased demand for complex procedures (e.g., liver transplantation, cerebral artery aneurysm clipping, aortic aneurysm repair) in patients previously considered at too high risk. Along with these expectations have come pressures on clinicians to reduce costs at the same time as improving clinical outcomes. Despite many advances in the care of critically ill patients with injury or sepsis, mortality, morbidity, and cost remain high;and nutritional support is frequently required. The duration and extent of the metabolic changes seen in response to critical surgical illness and intensive care treatments have became better characterized. Although some of the changes in body water and fat are modifiable, loss of large amounts of (functional) protein has been resistant to various strategies so far studied.

关键词：身体成分身体水份/代谢危重病人医疗危重病能量代谢营养支持蛋白质类/代谢脓毒症/代谢脓毒症/治疗创伤和损伤/代谢创伤和损伤/治疗人类

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Metabolic management of patients with severe burns

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WORLD JOURNAL OF SURGERY 2000年第6期24卷 673-680页

作者： Demling, RH Seigne, P Brigham & Womens Hosp Dept Surg Burn Ctr Boston MA 02115 USA Brigham & Womens Hosp Dept Anesthesia & Crit Care Boston MA 02115 USA

Burn injury results in profound metabolic abnormalities perpetuated by an exaggerated stress response to injury. Hypermetabolism and marked catabolism, with rapid erosion of lean body mass, becomes evident shortly after injury. Much of the morbidity and mortality of a major burn can be attributed to this process, which increases infection risks, decreases the healing rate, and alters cell function. Rapid removal of devitalized burn tissue combined with early aggressive nutritional support significantly attenuates this autodestructive process. The addition of anabolic agents decreases the degree of lean mass loss and increases the rate of restoration. Immediate attention to the metabolic response to a severe burn significantly decreases complications and improves outcome.

关键词：精氨酸/代谢烧伤/代谢烧伤/治疗脂肪酸类非酯化/代谢谷氨酰胺/代谢炎症/代谢微量营养系营养支持蛋白质类/代谢脓毒症/代谢睾酮/类似物和衍生物人类

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Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic circulation

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SURGERY 2000年第4期128卷 513-518页

作者： Zhao, HL Spain, DA Matheson, PJ Vaughn, C Harris, PD Garrison, RN Univ Louisville Dept Surg Louisville KY 40292 USA Univ Louisville Dept Physiol & Biophys Louisville KY 40292 USA Univ Louisville Ctr Excellence Appl Microcirculatory Res Louisville KY 40292 USA Vet Affair Med Ctr Louisville KY USA

Background. Altered intestinal bloodflow during systemic inflammation leads to organ dysfunction. Mucosal ischemia occurs during sepsis despite an increase in portal blood flow. We hypothesized that separate mechanisms are active in the large resistance and small mucosal microvessels to account for this dichotomy. Methods. Chronic infection was induced in rats by bacterial inoculation (Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge. Separate groups were studied at 24 and 72 hours after a single inoculation of bacterium or 24 hours after a second inoculation tie, 72 hours of sepsis). Time-matched controls were used for each group. Intravital microscopy of the terminal ileum was used to assess endothelial-dependent vasodilation to acetylcholine (10(-9) to 10(-5) mol/L) resistance (A(1)) and premucosal (A(3)) arterioles. Threshold sensitivity (-log of 20% response dose) was calculated from dose response curves for each animal. Results. Vasodilator sensitivity to acetylcholine in A(1) arterioles was significantly decreased at 24 hours, and these changes persisted up to 72 hours after a single bacterial inoculation. There was no change in the dilator sensitivity of A(3) arterioles after a single inoculation. When. there was a challenge with a second bacterial inoculation, there was a reversal of the A(1) dilator response and an increase in A(3) sensitivity. Conclusions. An initial septic event results in a decrease in dilator reactivity in the resistance A(1) arterioles that;persists for at least 72 hours. A sustained septic challenge results in increased dilator reactivity in both A(1) and A(3) vessels. This enhanced sensitivity during sepsis suggests that more than 1 therapeutic approach to preservation of intestinal bloodflow will be necessary.

关键词：乙酰胆碱/药理学拟杆菌感染/代谢拟杆菌感染/病理生理学拟杆菌脆弱大肠杆菌感染/代谢大肠杆菌感染/病理生理学肠黏膜/血液供给肠黏膜/酶学肠黏膜/病理生理学显微镜检查电视一氧化氮/代谢一氧化氮合酶/代谢大鼠 Sprague-Dawley 脓毒症/代谢脓毒症/病理生理学内脏循环/生理学血管舒张/药物作用血管舒张/生理学血管舒张药/药理学动物男(雄)性大鼠

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Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro

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JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1999年第1期134卷 49-55页

作者： Oberhoffer, M Stonans, I Russwurm, S Stonane, E Vogelsang, H Junker, U Jäger, L Reinhart, K Univ Jena Dept Anesthesiol & Intens Care Med D-07740 Jena Germany Univ Jena Inst Clin Immunol D-07740 Jena Germany

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear, Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT, Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation, Thus we demonstrate for the first time that PCT is expressed in PBMCs, This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.

关键词：抗原 CD14/分析碱基序列降钙素/血液降钙素/遗传学细胞因子类/药理学 DNA DNA引物基因表达调控/药物作用脂多糖类/药理学分子序列数据单核细胞/药物作用单核细胞/免疫学单核细胞/代谢肽碎片/血液植物血凝素类/药理学蛋白质前体/血液蛋白质前体/遗传学 RNA 信使/遗传学逆转录聚合酶链反应脓毒症/代谢人类

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Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects

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JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1999年第2期134卷 161-167页

作者： Braat, EAM Levi, M Bos, R Haverkate, F Lassen, MR de Maat, MPM Rijken, DC TNO Prevent & Hlth Gaubius Lab NL-2301 CE Leiden Netherlands Univ Amsterdam Acad Med Ctr Ctr Hemostasis Thrombosis Atherosclerosis & Infla NL-1105 AZ Amsterdam Netherlands Univ Copenhagen Hillerod Hosp Dept Orthopaed & Traumatol DK-1168 Copenhagen Denmark

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence of tcu-PA/T in human subjects with a varying degree of hypercoagulability, tcu-PA/T was assessed in the plasma of patients with disseminated intravascular coagulation (DIC), endotoxin-treated volunteers, patients with unstable angina pectoris, and patients selected for hip replacement, Relationships between tcu-PA/T and several markers reflecting thrombin generation were examined, tcu-PA/T was observed only in the plasma of patients with DIC and was associated with all thrombin markers and with scu-PA and urokinase antigen. Prothrombin fragment 1 + 2 and urokinase antigen were independent predictors of tcu-PA/T, The fact that tcu-PA/T could not be detected in the other three groups was explained by a lower extent of thrombin generation, a greater inhibition of thrombin by antithrombin, or less available urokinase antigen in these groups, The contribution of scu-PA to total urokinase antigen was decreased in the patients with DIC because of inactivation by thrombin, which may be an additional explanation for the inadequate fibrinolysis observed in these patients. These findings show that scu-PA can be inactivated in the circulation under severe pathophysiologic circumstances and that the process of inactivation depends not only on the generation of thrombin but also on the control of thrombin activity by its inhibitor antithrombin.

关键词：心绞痛/代谢关节成形术置换髋弥漫性血管内凝血/药物疗法弥漫性血管内凝血/代谢内毒素类/投药和剂量纤维蛋白溶解/药物作用纤维蛋白溶解/生理学止血药/投药和剂量止血药/代谢纤溶酶原激活剂/拮抗剂和抑制剂纤溶酶原激活剂/血液脓毒症/药物疗法脓毒症/代谢凝血酶/投药和剂量凝血酶/生物合成尿纤溶酶原激活物/拮抗剂和抑制剂尿纤溶酶原激活物/血液人类男(雄)性

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Changes in intermediary metabolism in severe surgical illness

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WORLD JOURNAL OF SURGERY 2000年第6期24卷 639-647页

作者： Wolfe, RR Martini, WZ Shriners Burns Hosp Metab Unit Galveston TX 77550 USA Univ Texas Med Branch Dept Surg Galveston TX 77550 USA

Under normal circumstances there is a reciprocal relation between the availability of free fatty acids (FFAs) and glucose in plasma. In the fasted state, FFAs predominate in both availability and the relative contribution to energy production, whereas the same is true for glucose in the fed state. The extent of glucose oxidation is directly determined by its availability, whereas FFAs are normally available well in excess of their rate of oxidation. The rate of FFA oxidation is determined by the rate of transfer into the mitochondria via the carnitine palmitoyltransferase (CPT) enzyme system, which in turn is regulated by the metabolism of glucose. With critical illness the stress response involves mobilization of both plasma glucose and FFAs simultaneously in both the fed and fasted states. In the situation of excess availability of substrates, the metabolism of glucose limits the oxidation of FFAs, thereby channeling those fatty acids into triglyceride (TG) stores in the muscle and the Liver. The high FFA concentrations and increased tissue TG stores can Limit glucose clearance from the blood, thereby contributing to the development of hyperglycemia. Also, the excessive metabolism of glucose can result in lacticacidemia and can contribute to the depletion of muscle glutamine. The nutritional treatment of such patients must account for these underlying metabolic responses to avoid amplifying potentially detrimental responses to the excess availability of substrates already present in the fasting stale.

关键词：酸中毒乳酸性/代谢脂肪组织/代谢危重病能量代谢/生理学脂肪酸类非酯化/血液脂肪酸类非酯化/代谢葡萄糖/代谢糖酵解高血糖症/代谢线粒体/代谢肌骨骼/代谢蛋白质类/代谢脓毒症/代谢外科手术人类

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低分子肝素对脓毒症大鼠腹主动脉内皮细胞蛋白C受体和蛋白酶活化受体1表达的影响

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中国医师杂志 2011年第5期13卷 621-623页

作者：李云峰蔡业平张圣岸戴新贵郴州市第一人民医院ICU 湖南省郴州423000 解放军总医院第一附属医院烧伤研究所

目的观察低分子肝素（LMWH）对脓毒症大鼠腹主动脉内皮细胞（VEC）蛋白C受体（EPCR）和蛋白酶活化受体1（PARl）表达的影响。方法采用组织贴块法培养24只Wister大鼠腹主动脉VEC，1：3传代至第4代，分为对照组（n=6）、脓毒症组（LPS1μg... 详细信息

目的观察低分子肝素（LMWH）对脓毒症大鼠腹主动脉内皮细胞（VEC）蛋白C受体（EPCR）和蛋白酶活化受体1（PARl）表达的影响。方法采用组织贴块法培养24只Wister大鼠腹主动脉VEC，1：3传代至第4代，分为对照组（n=6）、脓毒症组（LPS1μg／ml，n=6）、LMWH组（LPS1μg/ml＋LMWH5μg/ml，n=6）。分别在第1、3、5天采用流式细胞术（FCM）检测VEC表面的EPCR和PARl的表达。结果脓毒症组EPCR和PARl的表达各时间点均较对照组有明显下降（P〈0．05或P〈0．01），以第5天最为明显（26．53±7．21VS39．26±2．62，q=6．45，P〈0．01：53．214±15．10VS86．54±11．34，q=6．94，P〈0．01）。LMWH组EPCR和PARl的表达各时间点均高于脓毒症组（P〈0．05）；与对照组比较，EPCR在第1天仍有明显降低（40．86±1．63VS45．41.1±2．82，q=3．51，P〈0．05），但第3、5天接近对照组水平（41．20±3．32VS42．83±2．66，P〉0．05；39．23±3．33VS39．26±2．62，P〉0．05），PARl各时问点与对照组比较差异均无统计学意义（P〉0．05）。结论LMWH能有效改善脓毒症内皮细胞EPCR和PARl表达抑制的状态。

关键词：肝素低分子量/药理学脓毒症/代谢内皮细胞/代谢/药物作用蛋白质C/代谢受体 PAR一1/代谢

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