Objective

In sepsis, the protection of the vascular endothelium is essential and the maintenance of its function is critical to prevent further deterioration. High-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) is a bioactive lipid in plasma and its role in sepsis has not been extensively studied. This study aimed to investigate the effects of HDL-S1P on sepsis in cellular and animal models, as well as human plasma samples.

Measurements

We established an animal model of sepsis with different severities achieved by caecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection, and then explored the relationship between HDL-S1P and lung endothelial dysfunction in vivo. To determine the effects of HDL-S1P in the pulmonary endothelium of septic rats, we then injected HDL-S1P into septic rats to find out if it can reduce the lung injury caused by sepsis. Further, we explored the mechanism in vitro by studying the role of S1P-specific receptor agonists and inhibitors in LPS-stimulated human umbilical vein endothelial cells. We also explored the relationship between plasma HDL-S1P content and sepsis severity in septic patients by analysing their plasma samples.

Results

HDL-S1P concentrations in plasma were negatively correlated with endothelial functional damage in sepsis, both in the animal model and in the septic patients in our study. In vivo, HDL-S1P injection significantly reduced pulmonary oedema and endothelial leakage in septic rats. In vitro, cell experiments showed that HDL-S1P effectively protected the proliferation and migration abilities of endothelial cells, which could be partly explained by its biased activation of the S1P receptor 1.

Conclusion

Our study preliminary explored the function of HDL-S1P in sepsis in cellular and animal models, as well as human subjects. The results indicate HDL-S1P protected endothelial functions in septic patients. Thus, it has therapeutic potential and can be used for the clinical treatment of sepsis.

中文翻译：

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HDL-S1P在体内和体外保护脓毒症期间可保护内皮功能并减少肺部损伤。

目的

在脓毒症中，保护血管内皮至关重要，其功能的维持对于防止进一步恶化至关重要。高密度脂蛋白（HDL）相关的鞘氨醇-1-磷酸（S1P）是血浆中的一种生物活性脂质，其在败血症中的作用尚未得到广泛研究。这项研究旨在研究HDL-S1P对细胞和动物模型以及人类血浆样本中败血症的影响。

测量

我们通过盲肠结扎穿刺（CLP）和脂多糖（LPS）注射建立了具有不同严重程度的脓毒症动物模型，然后探讨了HDL-S1P与体内肺内皮功能障碍之间的关系。为了确定HDL-S1P在脓毒症大鼠肺内皮中的作用，我们将HDL-S1P注射到脓毒症大鼠中以了解其是否可以减轻败血症引起的肺损伤。此外，我们通过研究S1P特异性受体激动剂和抑制剂在LPS刺激的人脐静脉内皮细胞中的作用，探索了体外机制。通过分析血浆样本，我们还探讨了败血症患者血浆HDL-S1P含量与败血症严重程度之间的关系。

结果

在我们研究的动物模型和脓毒症患者中，血浆中HDL-S1P浓度与败血症中的内皮功能损害呈负相关。在体内，HDL-S1P注射可显着减少败血症大鼠的肺水肿和内皮细胞渗漏。在体外，细胞实验表明HDL-S1P有效地保护了内皮细胞的增殖和迁移能力，这在一定程度上可以归因于其对S1P受体1的偏向激活。

结论

我们的研究初步探讨了HDL-S1P在脓毒症中在细胞和动物模型以及人类受试者中的功能。结果表明，HDL-S1P保护败血症患者的内皮功能。因此，它具有治疗潜力，可用于脓毒症的临床治疗。