螺旋藻多糖在海水诱导急性肺损伤中的作用及机制研究

The mortality rate after near-drowning is extremely high, and it can be secondary to SWI-ALI/SWI-ARDS. The survival rate of near-drowning patients is still only one tenth, yet the pathogenesis of SWI-ALI/SWI-ARDS is unclear. At present, there are still no special effective drugs approved by the drug testing administration for ALI /ARDS. Marine polysaccharide drugs are rich in resources, good in biocompatibility, and have few toxic and side effects, which can be a breakthrough point to overcome some difficult diseases. Spirulina polysaccharide (SPS) has anti-oxidation, anti-coagulation, anti-inflammatory, and regulates the body's immunity and other biological activities, showing good application prospects. We have previously found that SPS can significantly drop off seawater-induced lung injury, reduce seawater-induced lung epithelial cells damage, and balance the secretion of oxidative stress-related factors. That makes SPS a potential hope for the treatment of seawater-induced lung injury, but its regulatory mechanisms have not been fully elucidated. Therefore, the project plans to have a further study on the effects of SPS on seawater-induced lung oxidative damage and its signaling pathways based on previous findings. The study included 1) determination of the effects of SPS on seawater-induced oxidative damage of lung epithelial cells; 2) determination of SPS to improve seawater-induced oxidative damage of lung epithelial cells by activating Nrf2-ARE signaling pathway; 3) determination of the regulation of SPS Nrf2-ARE signal pathway via MAPK and PI3K/AKT pathways. It provides a reliable theoretical basis for the treatment of seawater-induced lung injury by SPS, and new ideas and approaches to the study of the mechanism of seawater-induced lung injury. Moreover it will also offer the new ideas for the clinical application of SPS.

淹溺发生后死亡率高，可继发为SWI-ALI/ ARDS，发病机制不清，尚无任何药检局批准特效药物。海洋多糖药物可成为克服某些疑难病症的突破点。螺旋藻多糖（SPS）具有抗氧化、调节机体免疫力等生物活性，显示出良好的应用前景。我们前期研究发现SPS改善海水诱导的肺损伤，平衡氧化应激相关因子表达。成为治疗海水诱导肺损伤潜在希望，但其作用机制尚不明确。所以本项目计划进一步研究SPS对海水诱导肺损伤的作用及信号通路研究。研究内容包括1)确定SPS对海水诱导的肺上皮细胞氧化损伤的作用效果；2)确定SPS通过激活Nrf2-ARE信号通路改善海水诱导的肺上皮细胞氧化损伤；3)确定SPS通过MAPK及PI3K/AKT对Nrf2-ARE信号通路的调节作用。为SPS用于治疗海水诱导肺损伤提供可靠的理论依据，为海水诱导肺损伤机制研究提供新思路和途径，也为SPS临床应用提供新的思路。

海洋多糖药物资源丰富，生物兼容性良好，毒副作用小，可成为克服某些疑难病症的突破点。螺旋藻多糖具有抗氧化、抗凝血、抗炎、调节机体免疫力等功能，显示出良好的应用前景。淹溺发生后死亡率极高，可继发为ALI进而发展为ARDS，淹溺患者的生存率仍仅为十分之一，发病机制不清，目前世界上尚无任何药监局批准的针对ALI和ARDS的特效药物。我们的研究表明，螺旋藻多糖能显着减少海水引起的肺细胞损伤和凋亡，这为治疗这些重大疾病提供了新的希望，本项目探讨了螺旋藻多糖改善海水诱导的肺损伤的氧化应激通路，首次探讨了螺旋藻多糖通过激活Nrf2-ARE信号通路改善海水诱导的肺上皮细胞氧化损伤，并通过MAPK及PI3K/AKT对Nrf2-ARE信号通路进行调节。这些机制的阐明可为螺旋藻多糖治疗ALI/ARDS提供可靠的作用靶点，也为药物治疗ALI/ARDS提供新的靶点和治疗策略，更为螺旋藻多糖的潜在临床应用价值提供理论依据。