Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Department of Microbiology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Inflamm Res. 2019 Sep;68(9):723-726. doi: 10.1007/s00011-019-01255-7. Epub 2019 Jun 1.
Intestinal epithelial injury in septic patients predicts subsequent development of multiple organ failure, but its regulation by host factors remains unclear. Sphingosine kinase 1 is an enzyme-regulating inflammatory response.
Cecal ligation and puncture was used to induce sepsis in C57BL/6 mice with and without N,N-dimethylsphingosine, a SphK1 inhibitor. Symptom severity was monitored by murine sepsis severity score. The intestinal barrier function was determined using 4KDa fluorescein-dextran. Bacterial load in the bloodstream was determined by 16S rRNA gene amplification.
Our preliminary experimental data showed that expression of sphingosine kinase 1 in ileum was increased by sixfold in septic mice. Pharmacological blockade of sphingosine kinase 1 alleviated septic symptoms. The intestinal permeability and bacterial load in the bloodstream were also reduced in these animals. We hypothesized that inhibition of sphingosine kinase 1 may reduce pro-inflammatory cytokine production, and alleviate intestinal epithelial injury during sepsis. Further mechanistic studies and clinical specimen analyses are warranted.
脓毒症患者的肠道上皮损伤可预测随后发生多器官衰竭，但宿主因素对其的调节作用尚不清楚。鞘氨醇激酶 1 是一种调节炎症反应的酶。
使用盲肠结扎穿孔术在有和没有 N，N-二甲基鞘氨醇（鞘氨醇激酶 1 抑制剂）的 C57BL/6 小鼠中诱导脓毒症。通过小鼠脓毒症严重程度评分监测症状严重程度。使用 4kDa 荧光素葡聚糖测定肠道屏障功能。通过 16S rRNA 基因扩增测定血流中的细菌负荷。
我们的初步实验数据表明，脓毒症小鼠回肠中鞘氨醇激酶 1 的表达增加了 6 倍。鞘氨醇激酶 1 的药理学阻断可减轻脓毒症症状。这些动物的肠道通透性和血流中的细菌负荷也降低了。我们假设抑制鞘氨醇激酶 1 可能减少促炎细胞因子的产生，并减轻脓毒症期间的肠道上皮损伤。需要进一步的机制研究和临床标本分析。
