医学
弥漫性血管内凝血
脂质信号
败血症
多不饱和脂肪酸
调解人
凝结
免疫学
病理
脂肪酸
生物化学
炎症
内科学
生物
作者
Wenyan Zhang,Sneha Bhandari,Yi Ding,Jun Luo,Bo Feng,Yuchen Jiang,Ting Chen,Jinling Wei,Xiaodong Pan,Haixu Weng,Zhangna Ding,Jiawen Chen,Xi Chen,Yuqiang Gong,Hui Li,Shengwei Jin,Hao Yu
标识
DOI:10.1016/j.clnu.2024.04.020
摘要
Abstract
Background & Aims
Sepsis-induced disseminated intravascular coagulation (DIC) is characterized by abnormal blood clotting resulting from severe infection, contributing to organ dysfunction in sepsis. Resolvin D1 (RvD1) is an endogenous lipid mediator, synthesized from the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) through enzymatic processes involving 15-LOX and 5-LOX. RvD1 is recognised for its protective properties against various inflammatory conditions. This study aims to investigate its potential to modulate coagulation dysfunction in sepsis and to evaluate coagulation disorders in septic patients. Methods
Sepsis models were established by intraperitoneal injection LPS (20 mg/kg) or cecal ligation and puncture (CLP) followed by injection of RvD1 (10 μg/kg) or saline. The impact of RvD1 on coagulation dysfunction was assessed by clotting time and coagulation indicators such as TAT, D-dimer, PAI-1, and fibrinogen. The activity of the coagulation system in vivo was observed by evaluating dynamic microcirculation, platelets and thrombin in mice using intravital microscopy. The effect of RvD1 on pyroptosis was investigated by measuring NOD-like receptor protein 3 (NLRP3), Caspase-1, Caspase-11, and Gasdermin D (GSDMD) levels via western blot. Caspase-1 knockout mice, GSDMD knockout mice and bone marrow-derived macrophages (BMDMs) were used to elucidate the underlying mechanisms. Lastly, the concentration of RvD1 in plasma from septic patients was quantified to explore its relationship with coagulation and pyroptosis. Results
RvD1 significantly attenuated coagulation dysfunction in septic mice induced by LPS and CLP, and inhibited Caspase-1/GSDMD-dependent pyroptosis in septic mice and bone marrow-derived macrophages. In septic patients, the plasma concentrations of RvD1 was negatively correlated with both coagulation-related indicators and markers of GSDMD activation. Conclusion
The results suggest that RvD1 can improve coagulation dysfunction in sepsis by regulating the Caspase-1/GSDMD pyroptotic pathway. Additionally, the concentration of RvD1 in septic patient plasma is related to prognosis and DIC development. RvD1 could be a potential biomarker and a promising therapeutic alternative in sepsis-induced DIC.
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