Silica nanoparticles induced the pre-thrombotic state in rats via JNK-NF-κB/AP-1 pathway
Silica nanoparticles (SiNPs) play a vital role in medicine applications such as drug delivery and cancer therapy.SiNPs can translocate into bloodstream through all possible routes of entry.However, there is scarce study on pre-thrombotic effect of SiNPs and mechanism of pre-thrombotic state in vivo.We specifically focused on the changes of platelets function and blood coagulationin Wistar rats after consecutive 7 days” intravenous injectionof SiNPs (52 nm).The platelets aggregation assay, structural changes of platelets membrane glucoproteins, coagulation test, coagulant/anti-coagulant and fibrinolytic factors and the possible molecular mechanism of pre-thrombotic state formation were performed.Our results demonstrated a significant increase in platelets aggregation rate and platelet activation after SiNPs exposure.Clotting time were significantly shortened while fibrinogen (FIB) content was increased.There were sustained increases in coagulation factors and thrombin-antithrombin complex (TAT) expression induced by SiNPs.Antithrombin Ⅲ (AT-Ⅲ) of the SiNPs-treated groups were significantly decreased while concentrations of Tissue factor pathway inhibitor(TFPI), tissue plasminogen activator (t-PA)and D-dimer were elevated.The phosphorylation of nuclear factor-κB/p65 (NF-κB/p65) and activator protein-1/c-Jun (AP-1/c-Jun) and the protein levels of JNK were increased after SiNPs exposure.In summary, our results supported that SiNPscould induce the hypercoagulable and pre-thrombotic state in rats through the interaction between platelets activation, coagulation system hyperfunction and fibrinolytic system resistance.JNK-NF-κB/AP-1 pathway might be involved in regulation of pre-thrombotic state formation.
Toxicology Silica nanoparticles Pre-thrombotic state JNK-NF-κB/AP-1 pathway
Lizhen Jiang Weijia Geng Qiuling Li Zhiwei Sun Yanbo Li Yang Li Caixia Guo Yongbo Yu Yang Zou Yumei Yang Yang Yu Junchao Duan
School of Public Health,Capital Medical University, Beijing, 100069, P.R.China School of Public Health,Capital Medical University, Beijing, 100069, P.R.China;Beijing Key Laborator School of Public Health,Capital Medical University, Beijing, 100069, P.R.China;Novartis Institute Fo
国内会议
北京
英文
321-348
2015-06-01（万方平台首次上网日期，不代表论文的发表时间）