碲化镉量子点暴露对小鼠凝血相关因子的影响
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摘要
研究碲化镉量子点(cadmium telluride quantum dots, Cd Te QDs)对小鼠凝血相关因子的影响,进一步探讨QDs的心血管毒性机制。将48只雄性ICR小鼠随机分成6组,每组8只。分别使用不同剂量(0.15μmol·kg~(-1)、1.5μmol·kg~(-1)和15μmol·kg~(-1))的Cd Te QDs和生理盐水一次性经尾静脉注射染毒小鼠1 d,15μmol·kg~(-1)剂量的Cd Te QDs染毒3 d和7 d,检测小鼠血浆中凝血相关因子的含量变化。结果显示,与对照组相比,随着染毒剂量增加小鼠组织型纤溶酶原激活剂(t-PA)和纤维蛋白原(FIB)含量逐渐增高,组织因子途径抑制物(TFPI)含量逐渐降低,具有明显的剂量-效应关系。除15μmol·kg~(-1)剂量组外,组织因子(TF)、凝血因子XII(FXII)和纤溶酶原(Plg)含量具有升高的趋势,抗凝血酶Ⅲ(AT-Ⅲ)含量则无明显变化;随着染毒时间增加,TF、FXII、FIB、Plg和t-PA含量有明显的先升高后降低的变化趋势,TFPI含量在1 d达到最低,之后逐渐升高,AT-Ⅲ含量则在7 d达到最低。Cd Te QDs急性染毒可引起小鼠血浆中TF、FXII、FIB、TFPI、Plg和t-PA的含量明显改变,并且具有不同的变化趋势。提示Cd Te QDs可能会激活凝血系统和纤溶系统,抑制抗凝系统,从而引起凝血功能紊乱。
To study the effects of cadmium telluride quantum dots(CdTe QDs) on coagulation-related factors in mice, and to further explore the cardiovascular toxic mechanism of Cd Te QDs. 48 male ICR mice were randomly divided into 6 groups including 8 mice in each group. CdTe QDs with 0.15 μmol·kg~(-1), 1.5 μmol·kg-1 and 15 μmol·kg~(-1) were injected into mice for 1 d via tail vein, respectively. The exposure time of 15 μmol·kg~(-1) group was prolonged to 3 d and 7 d. Subsequently, the content changes of coagulation-related factors in mice was detected. The results showed that, compared with the control group, the content of tissue-type plasminogen activator(t-PA) and fibrinogen(FIB) increased gradually, whereas the content of tissue factor pathway inhibitor(TFPI) gradually de-creased with the increment of administrated dose, which showed a significant dose-effect relationship. In addition to the group of 15 μmol·kg~(-1) dose, the contents of tissue factor(TF), coagulation factor XII(FXII) and plasminogen(Plg) levels increased, but the content of antithrombin Ⅲ(AT-Ⅲ) did not change significantly. With the exposure time extending, the contents of TF, FXII, FIB and t-PA increased significantly at first and then decreased. The content of TFPI reached to the bottom at the 1 st d and then gradually increased. The content of AT-Ⅲ reached to the bottom at the 7 th d. Acute exposure to CdTe QDs can change the contents of TF, FXII, FIB, TFPI, Plg and t-PA in the plasma of mice significantly, and different trendency were found. These results suggested that CdTe QDs may activate the coagulation and fibrinolysis systems and inhibit the anticoagulation system. Therefore, coagulation dysfunction is caused.
To study the effects of cadmium telluride quantum dots(CdTe QDs) on coagulation-related factors in mice, and to further explore the cardiovascular toxic mechanism of Cd Te QDs. 48 male ICR mice were randomly divided into 6 groups including 8 mice in each group. CdTe QDs with 0.15 μmol·kg~(-1), 1.5 μmol·kg-1 and 15 μmol·kg~(-1) were injected into mice for 1 d via tail vein, respectively. The exposure time of 15 μmol·kg~(-1) group was prolonged to 3 d and 7 d. Subsequently, the content changes of coagulation-related factors in mice was detected. The results showed that, compared with the control group, the content of tissue-type plasminogen activator(t-PA) and fibrinogen(FIB) increased gradually, whereas the content of tissue factor pathway inhibitor(TFPI) gradually de-creased with the increment of administrated dose, which showed a significant dose-effect relationship. In addition to the group of 15 μmol·kg~(-1) dose, the contents of tissue factor(TF), coagulation factor XII(FXII) and plasminogen(Plg) levels increased, but the content of antithrombin Ⅲ(AT-Ⅲ) did not change significantly. With the exposure time extending, the contents of TF, FXII, FIB and t-PA increased significantly at first and then decreased. The content of TFPI reached to the bottom at the 1 st d and then gradually increased. The content of AT-Ⅲ reached to the bottom at the 7 th d. Acute exposure to CdTe QDs can change the contents of TF, FXII, FIB, TFPI, Plg and t-PA in the plasma of mice significantly, and different trendency were found. These results suggested that CdTe QDs may activate the coagulation and fibrinolysis systems and inhibit the anticoagulation system. Therefore, coagulation dysfunction is caused.
引文
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[15] Hu H, Asweto C O, Wu J, et al. Gene expression profiles and bioinformatics analysis of human umbilical vein endothelial cells exposed to PM2.5[J]. Chemosphere, 2017,183:589-598
[16] Tian Y, Zhao Y Y, Zheng W F, et al. Antithrombotic functions of small molecule-capped gold nanoparticles[J].Nanoscale, 2014, 6(15):8543-8550
[17] Yu X H, Zhao X Y, Ze Y G, et al. Changes of serum parameters of Ti O2, nanoparticle-induced atherosclerosis in mice[J]. Journal of Hazardous Materials, 2014, 280:364-371
[18] Ramot Y, Steiner M, Morad V, et al. Pulmonary thrombosis in the mouse following intravenous administration of quantum dot-labeled mesenchymal cells[J]. Nanotoxicology, 2010, 4(1):98-105
[2] Kairdolf B A, Smith A M, Stokes T H, et al. Semiconductor quantum dots for bioimaging and biodiagnostic applications[J]. Annual Review of Analytical Chemistry,2013, 6(1):143-162
[3]陈天琳.量子点电视的设计技术与发展现况分析[J].科学技术创新, 2018, 25:53-54Chen T L. The analysis of the design and development of quantum dots television[J]. Scientific and Technological Innovation, 2018, 25:53-54(in Chinese)
[4] Meng P J, Xiong Y M, Wu Y T, et al. A novel strategy to evaluate the degradation of quantum dots:Identification and quantification of Cd Te quantum dots and corresponding ionic species by CZE-ICP-MS[J]. Chemical Communications, 2018, 54(42):5342-5345
[5] Luo Y H, Wu S B, Wei Y H, et al. Cadmium-based quantum dot induced autophagy formation for cell survival via oxidative stress[J]. Chemical Research in Toxicology,2013, 26(5):662-673
[6] Peng L, He M, Chen B, et al. Cellular uptake, elimination and toxicity of Cd Se/ZnS quantum dots in Hep G2 cells[J]. Biomaterials, 2013, 34(37):9545-9558
[7] Wang J L, Sun H B, Meng P J, et al. Dose and time effect of Cd Te quantum dots on antioxidant capacities of the liver and kidneys in mice[J]. International Journal of Nanomedicine, 2017, 12:6425-6435
[8] Khalil W K B, Girgis E, Emam A N, et al. Genotoxicity evaluation of nanomaterials:DNA damage, micronuclei,and 8-hydroxy-2-deoxyguanosine induced by magnetic doped Cd Se quantum dots in male mice[J]. Chemical Research in Toxicology, 2011, 24(5):640-650
[9] Nemmar A, Hoet P H, Vanquickenborne B, et al. Passage of inhaled particles into the blood circulation in humans[J]. Circulation, 2002, 105(4):411-414
[10]王书美,李秋月,林治卿,等.纳米颗粒物呼吸暴露致心血管系统损伤的硝化应激作用及可能机制[J].环境与健康杂志, 2017, 34(12):1111-1116Wang S M, Li Q Y, Lin Z Q, et al. Nitrosative stress as a signaling pathway for cardiovascular damage induced by nanoparticles inhalation:A review of recent studies[J].Journal of Environment and Health, 2017, 34(12):1111-1116(in Chinese)
[11] Baccarelli A, Martinelli I, Zanobetti A, et al. Exposure to particulate air pollution and risk of deep vein thrombosis[J]. Archives of Internal Medicine, 2008, 168(9):920-927
[12] Nemmar A, Albarwani S, Beegam S, et al. Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation[J]. International Journal of Nanomedicine, 2014, 9(2):2779-2789
[13] Rückerl R, Ibaldmulli A, Koenig W, et al. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease[J]. American Journal of Respiratory and Critical Care Medicine, 2006, 173(4):432-441
[14]寇璐璐,康少伟,刘兰博,等.不同浓度可吸入颗粒物对2型糖尿病大鼠凝血纤溶因子的影响[J].中国糖尿病杂志, 2015, 23(7):647-649Kou L L, Kang S W, Liu L B, et al. Study on the blood coagulation FIB rinolytic factors in type 2 diabetic rats exposed to different dose of PM2.5[J]. Chinese Journal of Diabetes, 2015, 23(7):647-649(in Chinese)
[15] Hu H, Asweto C O, Wu J, et al. Gene expression profiles and bioinformatics analysis of human umbilical vein endothelial cells exposed to PM2.5[J]. Chemosphere, 2017,183:589-598
[16] Tian Y, Zhao Y Y, Zheng W F, et al. Antithrombotic functions of small molecule-capped gold nanoparticles[J].Nanoscale, 2014, 6(15):8543-8550
[17] Yu X H, Zhao X Y, Ze Y G, et al. Changes of serum parameters of Ti O2, nanoparticle-induced atherosclerosis in mice[J]. Journal of Hazardous Materials, 2014, 280:364-371
[18] Ramot Y, Steiner M, Morad V, et al. Pulmonary thrombosis in the mouse following intravenous administration of quantum dot-labeled mesenchymal cells[J]. Nanotoxicology, 2010, 4(1):98-105