Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock.
Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock.
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DOI：
10.1213/ane.0b013e318210385c
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发表时间：
2011-06
影响因子：
5.7
通讯作者：
Paredes A
中科院分区：
文献类型：
--
作者：
Kozar RA;Peng Z;Zhang R;Holcomb JB;Pati S;Park P;Ko TC;Paredes A
对创伤失血性休克患者使用基于血浆的复苏与死亡率降低相关。虽然有些人提出了通过替代凝血蛋白的有益作用，但血浆提供的假定保护机制尚不清楚。我们之前已经在细胞培养模型中表明，与晶体相比，血浆降低了内皮细胞的通透性。内皮糖萼由蛋白聚糖和糖蛋白组成，它们附着在多配体聚糖骨架上，共同保护下面的内皮。我们推测，血浆对内皮细胞的保护作用部分是由于其在失血性休克后恢复了内皮糖萼和保存了多配体蛋白聚糖-1。使大鼠失血性休克至平均动脉血压30 mmHg持续90分钟，随后用乳酸林格氏溶液（LR）或新鲜血浆复苏至平均动脉血压80 mmHg，并与假手术或单独休克进行比较。两小时后，收获肺用于多配体蛋白聚糖mRNA，用抗多配体蛋白聚糖-1免疫染色，或用苏木精和伊红染色。为了具体检查血浆对内皮的影响，用镧基溶液输注小肠肠系膜，鉴定小静脉，并通过电子显微镜观察糖萼。所有数据均以平均值±SEM表示。通过单向方差分析和Tukey事后检验分析结果。电子显微镜显示出血性休克后糖萼的降解，血浆可部分恢复，但LR不能。与单独休克（1.39 ± 0.22）或LR（0.82 ± 0.03）相比，用血浆复苏的动物的肺syndecan-1 mRNA表达更高（2.76 ± 0.03），并且与细胞表面syndecan-1免疫染色相关。休克还导致了显著的肺损伤，组织病理学评分为（1.63 ± 0.26），用血浆复苏（0.67 ± 0.17）而不是LR（2.0 ± 0.25）减轻了该损伤。血浆的保护作用可能部分归因于其在失血性休克后恢复内皮糖萼和保存多配体蛋白聚糖-1的能力。
The use of plasma-based resuscitation for trauma patients in hemorrhagic shock has been associated with a decrease in mortality. While some have proposed a beneficial effect through replacement of coagulation proteins, the putative mechanisms of protection afforded by plasma are unknown. We have previously shown in a cell culture model that plasma decreases endothelial cell permeability compared to crystalloid. The endothelial glycocalyx consists of proteoglycans and glycoproteins attached to a syndecan backbone, which together protect the underlying endothelium. We hypothesize that endothelial cell protection by plasma is due, in part, to its restoration of the endothelial glycocalyx and preservation of syndecan-1 after hemorrhagic shock. Rats were subjected to hemorrhagic shock to a mean arterial blood pressure of 30 mmHg for 90 minutes followed by resuscitation with either lactated Ringer’s solution (LR) or fresh plasma to a mean arterial blood pressure of 80 mm Hg and compared to shams or shock alone. After two hours, lungs were harvested for syndecan mRNA, immunostained with anti-syndecan-1, or stained with hematoxylin and eosin. To specifically examine the effect of plasma on the endothelium, small bowel mesentery was infused with a lanthanum-based solution, venules identified, and the glycocalyx visualized by electron microscopy. All data are presented as mean ±SEM. Results were analyzed by one-way ANOVA with Tukey post hoc tests. Electron microscopy revealed degradation of the glycocalyx after hemorrhagic shock which was partially restored by plasma but not LR. Pulmonary syndecan-1 mRNA expression was higher in animals resuscitated with plasma (2.76 ± 0.03) compared to shock alone (1.39 ± 0.22) or LR (0.82 ± 0.03) and correlated with cell surface syndecan-1 immunostaining. Shock also resulted in significant lung injury by histopathology scoring (1.63 ± 0.26) which was mitigated by resuscitation with plasma (0.67 ± 0.17) but not LR (2.0 ± 0.25). The protective effects of plasma may be due in part to its ability to restore the endothelial glycocalyx and preserve syndecan-1 after hemorrhagic shock.