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硅纳米粒子和醋酸铅共同暴露对心血管系统的亚急性毒性。

Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system.

机构信息

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China,

Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China,

出版信息

Int J Nanomedicine. 2018 Nov 21;13:7819-7834. doi: 10.2147/IJN.S185259. eCollection 2018.

Abstract

BACKGROUND

The harmful effects following the release of nanomaterials into environment are of great concern today.

PURPOSE

In this study, subacute effect due to co-exposure to low-dose silica nanoparticles (SiNPs) and lead acetate (Pb) on cardiovascular system was detected in Sprague Dawley male rats.

MATERIALS AND METHODS

Histopathological and ultrastructural changes of heart, aortic arch and abdominal aorta were detected. Blood routine and blood biochemistry examinations were used to show the changes of blood components. The fibrinolytic and plasmin factors, inflammation-related factors and myocardial-related enzyme in serum were analysised by ELISA and Western blot assay.

RESULTS

Histopathological and ultrastructural examination of heart, aortic arch, and abdominal aorta showed that serious damage occurred in co-exposure group (n=6/group). Blood routine examination showed that leukocytosis and thrombocytopenia increased markedly, while changes in the erythrocyte count were not obvious in the co-exposure group. The expression of alanine transaminase (ALT) decreased obviously in co-exposure group, while no significant changes were noted in the expression of aspartate aminotransferase (AST), cholesterol (CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the co-exposure group on blood biochemistry analysis. In addition, data from ELISA analysis showed that the levels of fibrinolytic and plasmin factors, including thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), tissue-type plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and antithrombin III (AT III), were decreased, while those of human fibrinogen (FIB) and D-dimer (D2D) increased significantly in the co-exposure group. Moreover, the myocardial-related enzyme in serum, tested by ELISA, and cardiovascular-related protein expression of atrial natriuretic peptide and brain natriuretic peptide, tested by Western blot assay, was increased in the heart. Furthermore, the expression of inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was increased in heart tissue subjected to combined exposure, which was manifested by Western blot assay, while the protein levels of angiotensin II (ANG II) and endothelin 1 were (ET-1) elevated in blood vessels in the co-exposure group.

CONCLUSION

In conclusion, the major interactions involved in subacute toxicity due to co-exposure to low doses of SiNPs and Pb on cardiovascular system were expected to be additive and synergistic in nature. Co-exposure to SiNPs and Pb could aggravate the cardiovascular toxicity via endothelial damage, hypercoagulation, and cardiac injury in vivo.

摘要

背景

纳米材料释放到环境中所产生的有害影响是当今人们关注的焦点。

目的

本研究旨在检测低剂量二氧化硅纳米颗粒(SiNPs)和醋酸铅(Pb)共同暴露对 Sprague Dawley 雄性大鼠心血管系统的亚急性影响。

材料与方法

检测心脏、主动脉弓和腹主动脉的组织病理学和超微结构变化。采用血常规和血液生化检查检测血液成分的变化。采用 ELISA 和 Western blot 检测血清中纤维蛋白溶解和纤溶因子、炎症相关因子和心肌相关酶。

结果

心脏、主动脉弓和腹主动脉的组织病理学和超微结构检查显示,共同暴露组(n=6/组)出现严重损伤。血常规检查显示白细胞增多和血小板减少明显,而共同暴露组红细胞计数变化不明显。共同暴露组丙氨酸转氨酶(ALT)表达明显降低,而天门冬氨酸转氨酶(AST)、胆固醇(CHO)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)在血液生化分析中表达无明显变化。此外,ELISA 分析数据显示,纤维蛋白溶解和纤溶因子的水平,包括凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、组织型纤溶酶原激活物(t-PA)、组织因子途径抑制剂(TFPI)和抗凝血酶 III(AT III)降低,而共同暴露组中人纤维蛋白原(FIB)和 D-二聚体(D2D)显著升高。此外,ELISA 检测血清中心肌相关酶,Western blot 检测心房利钠肽和脑利钠肽的心血管相关蛋白表达,均增加。此外,Western blot 检测显示,共同暴露组心脏组织中炎症因子如 C 反应蛋白(CRP)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达增加,血管中血管紧张素 II(ANG II)和内皮素 1(ET-1)的蛋白水平升高。

结论

综上所述,低剂量 SiNPs 和 Pb 共同暴露对心血管系统亚急性毒性的主要相互作用可能具有相加和协同作用。SiNPs 和 Pb 的共同暴露可能通过体内内皮损伤、血液高凝和心脏损伤加重心血管毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/befe/6257131/9c2fd719d52a/ijn-13-7819Fig1.jpg

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