Michael and Marian Ilitch Department of Surgery, Wayne State University, Detroit, MI.
Michael and Marian Ilitch Department of Surgery, Wayne State University, Detroit, MI.
Surgery. 2022 Mar;171(3):825-832. doi: 10.1016/j.surg.2021.08.068. Epub 2021 Dec 2.
Hemorrhagic shock leads to endothelial glycocalyx shedding, endothelial cellular inflammation, and increased vascular permeability. Early plasma administration improves survival in severely injured patients; this may be due in part to its ability to ameliorate this trauma-induced endotheliopathy. The protective effect of early plasma administration may be due to its sphingosine 1-phosphate content. Principle carriers of plasma sphingosine 1-phosphate include apolipoprotein M and albumin. The relative roles of these carriers on sphingosine 1-phosphate protective effects are unknown and were studied in an in vitro model of microcirculation.
Endothelial cell monolayers were established in microfluidic perfusion devices and exposed to control or biomimetic shock conditions. Sphingosine 1-phosphate, albumin + sphingosine 1-phosphate, or apolipoprotein M + sphingosine 1-phosphate were added later to the perfusate. Biomarkers of endothelial and glycocalyx activation and damage were then determined.
Sphingosine 1-phosphate preserved endothelial and glycocalyx barrier function after exposure to conditions of shock in the microcirculation. The protective effect was related to sphingosine 1-phosphate chaperones; the apolipoprotein M loaded with sphingosine 1-phosphate had the most profound effect.
Carrier-based sphingosine 1-phosphate may be a useful adjunct in early hemorrhagic shock resuscitation.
出血性休克会导致内皮糖萼脱落、内皮细胞炎症和血管通透性增加。早期输注血浆可提高严重创伤患者的生存率；这可能部分归因于其改善创伤性内皮病变的能力。早期输注血浆的保护作用可能与其 1-磷酸鞘氨醇（S1P）含量有关。血浆 1-磷酸鞘氨醇的主要载体包括载脂蛋白 M 和白蛋白。这些载体在 1-磷酸鞘氨醇保护作用中的相对作用尚不清楚，并在体外微循环模型中进行了研究。
在微流控灌注装置中建立内皮细胞单层，并暴露于对照或仿生休克条件下。随后将 1-磷酸鞘氨醇、白蛋白+1-磷酸鞘氨醇或载脂蛋白 M+1-磷酸鞘氨醇添加到灌流液中。然后测定内皮细胞和糖萼激活和损伤的生物标志物。
1-磷酸鞘氨醇可维持微循环休克后内皮细胞和糖萼屏障功能。保护作用与 1-磷酸鞘氨醇伴侣有关；载脂蛋白 M 负载的 1-磷酸鞘氨醇具有最显著的作用。
基于载体的 1-磷酸鞘氨醇可能是早期出血性休克复苏的有用辅助手段。
