Dieterich Hans-Jürgen, Weissmüller Thomas, Rosenberger Peter, Eltzschig Holger K
Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
Crit Care Med. 2006 Jun;34(6):1775-82. doi: 10.1097/01.CCM.0000218814.77568.BC.
Several studies have suggested that intravenous hydroxyethyl starch treatment may dampen acute inflammatory responses. It is well documented that limited oxygen delivery to tissues (hypoxia) is common in acute inflammation, and numerous parallels exist between acute responses to hypoxia and to inflammation, including the observation that both are associated with increased vascular leakage and neutrophil infiltration of tissues. Therefore, we compared functional influences of hydroxyethyl starch on normoxic or posthypoxic endothelia.
Laboratory study.
University hospital.
Cultured human microvascular endothelial cells and mice (C57BL/6/129 svj).
We measured functional influences of hydroxyethyl starch on normoxic or posthypoxic endothelia.
Studies to assess endothelial barrier function in vitro indicated that the addition of hydroxyethyl starch promotes endothelial barrier in a dose-dependent fashion and hydroxyethyl starch-barrier effects are increased following endothelial hypoxia exposure (human microvascular endothelial cells, 48 hrs, 2% oxygen). Treatment of human microvascular endothelial cells with hydroxyethyl starch resulted in a dose-dependent increase in 157-phosphorylated vasodilator-stimulated phosphoprotein, a protein responsible for controlling the geometry of actin-filaments. Neutrophil adhesion was decreased in the presence of physiologically relevant concentrations of hydroxyethyl starch in vitro, particularly after endothelial hypoxia exposure. Using a murine model of normobaric hypoxia, increases in vascular leakage and pulmonary edema associated with hypoxia exposure (4 hrs at 8% oxygen) were decreased in animals treated with intravenous hydroxyethyl starch. Increases of tissue neutrophil accumulation following hypoxia exposure were dampened in hydroxyethyl starch-treated mice.
Taken together, these results indicate that hypoxia-induced increases in vascular leakage and acute inflammation are attenuated by hydroxyethyl starch treatment.
多项研究表明，静脉注射羟乙基淀粉治疗可能会抑制急性炎症反应。有充分文献记载，在急性炎症中，组织的氧输送受限（缺氧）很常见，并且对缺氧和炎症的急性反应之间存在许多相似之处，包括二者均与血管渗漏增加和组织中的中性粒细胞浸润有关的观察结果。因此，我们比较了羟乙基淀粉对常氧或缺氧后内皮细胞的功能影响。
实验室研究。
大学医院。
培养的人微血管内皮细胞和小鼠（C57BL/6/129 svj）。
我们测量了羟乙基淀粉对常氧或缺氧后内皮细胞的功能影响。
体外评估内皮屏障功能的研究表明，添加羟乙基淀粉以剂量依赖的方式促进内皮屏障，并且在内皮细胞缺氧暴露后（人微血管内皮细胞，48小时，2%氧气）羟乙基淀粉的屏障作用增强。用羟乙基淀粉处理人微血管内皮细胞导致157-磷酸化血管舒张刺激磷蛋白剂量依赖性增加，该蛋白负责控制肌动蛋白丝的几何形状。在体外存在生理相关浓度的羟乙基淀粉时，中性粒细胞黏附减少，尤其是在内皮细胞缺氧暴露后。使用常压缺氧小鼠模型，静脉注射羟乙基淀粉治疗的动物中，与缺氧暴露（8%氧气下4小时）相关的血管渗漏和肺水肿增加有所减少。在羟乙基淀粉处理的小鼠中，缺氧暴露后组织中性粒细胞积聚的增加受到抑制。
综上所述，这些结果表明，羟乙基淀粉治疗可减轻缺氧诱导的血管渗漏增加和急性炎症。
