磁性纳米颗粒体外致栓性的研究

目的通过探讨体外不同浓度50am葡聚糖包裹磁性纳米材料的致栓性，评价其作为药物载体的发伞性。方法以PBS为对照组，将0．02mg／ml、0．1mg／ml、0．5mg／ml浓度的磁性纳米颗粒与血浆或全血在体外共孵育，检测血小扳聚集率、凝血功能、血凝块质量及血栓弹力图。结果（1）PBS组、0．02mg／ml SPIO组、0．1mg／ml SPIO组及0．5mg／ml SPIO组血小板聚集率分别为67．3±5．9％、68．3±4．5％、66．2±5．5％及69．5±5．9％（P〉0．05）；（2）4组的APTT值分别为28．1±2．7S、28．5±2．4S、28．2±2．5S及29．1±3．6S（P〉0．05），PT值和TT值各组间也无统计学差异（P〉0．05）。（3）血栓弹力图各参数（反应凝血功能的R时间、反应纤维蛋自原功能的K时间及α角、反应血小板功能的MA值、凝血综合指数CI），各组间比较差异均无显著性（P〉0．05）。（4）4组的血凝块质量分别为759．6±38．7mg、758.8±47．2mg、769．8±39．2mg和766．8±40．8mg，组问比较无统计学差异（P〉0．05）。结论50nm葡聚糖包裹磁性纳米材料在一定浓度范围内（0．02mg／ml-0．5mg／ml）对血小板聚集、凝血功能、血凝块质量及血栓弹力图均无明显影响，表明其无致栓性．血液相容性较好，可较为安全的应用于血栓性疾病的研究。

Thrombogenicity of Superparamagnetic Iron Oxide Nanoparticles in Vitro

Objective To explore the thrombogenicity of 50 nm dextran superparamagnetic iron oxide nanoparticles（SPIO） in vitro, and to deduce the safety of the SPIO as drug carrier. Methods The characterization of SPIO was measured. Size distrubution and surface charge were determined by dynamic light scattering （DLS） and electrophoretic light scattering （ELS）, respectively. Size and morphology were measured by transmission electron microscopy（TEM） and scanning electron microscope（SEM）. Different concentrations of SPIO were mixed with test plasma or whole blood. The resulting solution was incubated at 37℃ for 30min or at room temperature for 40min. Platelet aggregation, plasma coagulation time, thrombelastogram and quality of blood clot were analyzed to determine the thrombogenicity of SPIO. The tendency to cause platelet aggregation or perturb plasma coagulation in vitro served as the indication of SPIO＇s thrombogenicity in vivo. Results （1）Platelet aggregation rates in PBS group, 0.02 mg/ml SPIO group, 0.1 mg/ml SPIO group and 0.5 mg/ml SPIO group were 67.3 ±5.9 %, 68.3 ± 4.5 %, 66.2± 5.5 % and 69.5 ± 5.9 %, suggesting that SPIO did not activate platelets under the tested condition（P〉0.05）.（2）APTT of the four groups were 28.1±2.7 S, 28.5±2.4 S, 28.2±2.5 S and 29.1±3.6 S（P〉0.05）. Also there was no significant difference in PT or TT between groups（P〉0.05）. （3） For the parameters of thromboelastography （ R time presented coagulation time, K time and α angle for function of fibrinogen, MA for platelet function, and coagulation index CI）, there was no significant difference between groups （P〉 0.05）. （4） Quality of blood clots of the four groups were 759.6±38.7 mg, 758.8±47.2 nag, 769.8±39.2 mg and 766.8±40.8 mg, demonstrating SPIO did not change the quality of blood clots in vitro at concentrations up to 0.5 mg/ml（P〉0.05）. For different concentrations of SPIO, there was no difference in platelat aggregation, plasma coagulation time, thrombelastogram or quality of blood clot（P〈0.05）. Conclusions The SPIO had no effect on platelet aggregation or plasma coagulation in vitro, suggesting little likelihood of SPIO to be thrombogenic in vivo and elucidating the safety of SPIO as drug carrier used in thrombotic diseases.