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[炎症过程中的微循环与止血。通过给予生理性蛋白酶抑制剂进行调节作为一种治疗方法]

[Microcirculation and hemostasis in inflammatory processes. Modulation by administration of physiologic protease inhibitors as a therapeutic approach].

作者信息

Leithäuser B, Matthias F R

机构信息

Zentrum für Innere Medizin, Justus-Liebig-Universität, Medizinische Klinik I, Giessen.

出版信息

Med Klin (Munich). 1997 Jul 15;92(7):426-31. doi: 10.1007/BF03042575.

DOI:10.1007/BF03042575
PMID:9324629
Abstract

BACKGROUND

The course of an inflammatory process is based upon complex interactions between the vessel wall and the humoral or cellular compounds of the vascular content as a consequence of a defense reaction. There are no substantial differences between the pathophysiology of local or of whole body inflammation on the molecular and cellular level. Sepsis, which is clinically regarded as a systemic inflammatory process requires the broad therapeutical spectrum of nowaday intensive care medicine, but still has a high mortality. The pathophysiology and clinical examples for both systemic and local inflammatory reactions are presented in this paper. Thereby, similar interactions between the vascular endothelium, the mediator systems to which the hemostatic system has to be considered as a part of, and the microcirculation remain in the foreground at first. Based on that, the use of polyvalent protease inhibitors in the therapy of local or systemic inflammatory reactions of different origin will be discussed. The spotlight falls on physiological inhibitors of the hemostatic and complement system, antithrombin III and C1-esterase inhibitor, which may have a regulatory function within these systems because of their multiple targets.

CONCLUSION

The possibility of an adjuvant therapy of local or generalized inflammatory processes with physiologic protease inhibitors seems to be very promising. Nevertheless, at yet the substantial mechanisms of action are not fully understood.

摘要

背景

炎症过程基于血管壁与作为防御反应结果的血管内容物的体液或细胞成分之间的复杂相互作用。在分子和细胞水平上,局部炎症或全身炎症的病理生理学没有实质性差异。脓毒症在临床上被视为全身性炎症过程,需要当今重症监护医学广泛的治疗范围,但死亡率仍然很高。本文介绍了全身和局部炎症反应的病理生理学及临床实例。因此,血管内皮、必须将止血系统视为一部分的介质系统以及微循环之间的相似相互作用首先成为关注焦点。基于此,将讨论多价蛋白酶抑制剂在治疗不同起源的局部或全身炎症反应中的应用。重点关注止血和补体系统的生理抑制剂,抗凝血酶III和C1酯酶抑制剂,由于它们具有多个靶点,可能在这些系统中具有调节功能。

结论

用生理蛋白酶抑制剂辅助治疗局部或全身性炎症过程的可能性似乎很有前景。然而,目前其主要作用机制尚未完全了解。

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本文引用的文献

1
Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Possible indication of the degree of endothelial cell activation?临床诊断脓毒症发作时患者的止血异常与疾病严重程度。内皮细胞激活程度的可能指标?
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Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III.抗凝血酶III对内毒素诱导的肺血管损伤的减轻作用。
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Coagulation inhibitor substitution during sepsis.
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Is sepsis a mediator-inhibitor mismatch?脓毒症是一种介质-抑制剂不匹配的情况吗?
Intensive Care Med. 1995 Nov;21 Suppl 2:S250-7. doi: 10.1007/BF01740763.
6
Microvascular effects of complement blockade with soluble recombinant CR1 on ischemia/reperfusion injury of skeletal muscle.可溶性重组补体受体1阻断补体对骨骼肌缺血/再灌注损伤的微血管效应
J Immunol. 1993 Jun 1;150(11):5104-13.
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Effects of leukocyte activation on capillary hemodynamics in skeletal muscle.
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Reduction of mortality with antithrombin III in septicemic rats: a study of Klebsiella pneumoniae induced sepsis.抗凝血酶III降低败血症大鼠死亡率的研究:肺炎克雷伯菌诱导败血症的研究
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Guidelines for the use of innovative therapies in sepsis.脓毒症创新疗法使用指南
Crit Care Med. 1993 Mar;21(3):476-7. doi: 10.1097/00003246-199303000-00032.
10
Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation.抗凝血酶III浓缩物用于伴有弥散性血管内凝血的感染性休克的双盲、安慰剂对照试验。
Chest. 1993 Sep;104(3):882-8. doi: 10.1378/chest.104.3.882.