The mechanism study on silica nanoparticles-induced blood hypercoagulable state and thrombus formation
作者单位：Department of Toxicology and Sanitary Chemistry School of Public Health Capital Medical University Beijing Key Laboratory of Environmental Toxicology Capital Medical University
会议名称：《中国毒理学会第七次全国会员代表大会暨中国毒理学会第六次中青年学者科技论坛》
会议日期：2018年
学科分类：100405[医学-卫生毒理学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0702[理学-物理学] 10[医学]
关 键 词：Silica nanoparticles inflammation-coagulation cascade thrombus formation
摘 要：Silica nanoparticles (Si NPs) are widely applied in food sciences, industry and biomedicine, which greatly increase the human exposure and potential health risk. However, the effect of Si NPs on circulation system, especially on thrombus formation was largely *** study was aimed to explore the adverse effect of Si NPs on thrombus formation, and to elucidate the underlying mechanisms in zebrafish (Danio rerio). Using transgenic lines,Tg(mpo:GFP) and Tg(fli-1:EGFP) zebrafish, the activation of neutrophils-mediated inflammation and impairment of vascular endothelium were detected in caudal vein of zebrafish induced by Si NPs. The blood flow and blood velocity decreased significantly via ZebraBlood analysis,reflecting the haemodynamic changes triggered by Si NPs. The thrombus formation in Si NPstreated zebrafish embryos was markedly increased by erythrocytes staining. Based on microarray and bioinformatics analysis, JAK1/TF/PAR1 signaling pathway was verified by qRT-PCR and Western blot assay. For in-deep study, the il6st and f2r were knocked down with specific morpholinos (MO). Whole-mount in situ hybridization and qRT-PCR analysis showed that the expression jak1 and f3b were attenuated in il6st knockdown groups;while knockdown of f2r effective declined the fga expression induced by Si NPs. Knockdown of f2r also caused the inhibition of fibrinogen expression and thrombus formation. In summary, our data demonstrated that Si NPs induced inflammation-coagulation cascade, blood hypercoagulable state and thrombus formation via JAK1/TF/PAR1 signaling pathway;il6st and f2r are critical molecular targets forSi NPs-induced thrombus formation.