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.
Core Facility Centre, Capital Medical University, Beijing 100069, PR China.
Sci Total Environ. 2019 May 1;663:245-253. doi: 10.1016/j.scitotenv.2019.01.346. Epub 2019 Jan 28.
Epidemiological evidence suggests that fine particulate matter (PM) in air pollution promotes the formation of deep venous thrombosis. However, no evidence is available on the effects of PM lead to disseminated intravascular coagulation (DIC). For the first time, this study explored the effects of PM on DIC via coagulation disorders in vivo. SD rats received intratracheal instillation of PM once every three days for one month. Doppler ultrasound showed that the pulmonary valve (PV) and aortic valve (AV) peak flow were decreased after exposure to PM. Fibrin deposition and bleeding were observed in lung tissue and vascular endothelial injury was found after exposure to PM. Expression of thrombomodulin (TM) in vessel was downregulated after PM-treated, whereas the levels of proinflammatory factors and adhesion molecules (IL-6, IL-1β, CRP, ICAM-1 and VCAM-1) were markedly elevated after exposure to PM. Tissue factor (TF) and the coagulation factor of FXa were increased, while vWF was significantly lowered induced by PM. Thrombin-antithrombin complex (TAT) and fibrinolytic factor (t-PA) were elevated, while there was no significantly change in the expression of anticoagulant factors (TFPI and AT-III). To clarify the relationship between PM and DIC, we examined the general diagnostic indices of DIC: PM prolonged PT and increased the expression of D-dimer but decreased platelet count and fibrinogen. In addition, the gene levels of JAK1 and STAT3 showed an upward trend, whereas there was little effect on JAK2 expression. And inflammatory factors (IL-6, IL-1β and TNF) in blood vessels of were up-reglated in PM-treated rats. In summary, our results found that PM could induce inflammatory response, vascular endothelial injury and prothrombotic state, eventually resulted in DIC. It will provide new evidence for a link between PM and cardiovascular disease.
流行病学证据表明，空气污染中的细颗粒物（PM）促进深静脉血栓形成。然而，目前尚无证据表明 PM 会导致弥散性血管内凝血（DIC）。本研究首次通过体内凝血紊乱探讨了 PM 对 DIC 的影响。SD 大鼠每隔三天经气管内滴注 PM 一次，共一个月。多普勒超声显示，PM 暴露后肺动脉瓣（PV）和主动脉瓣（AV）峰值流量降低。PM 暴露后肺组织可见纤维蛋白沉积和出血，血管内皮损伤。PM 处理后血管中血栓调节蛋白（TM）的表达下调，而促炎因子和黏附分子（IL-6、IL-1β、CRP、ICAM-1 和 VCAM-1）的水平在 PM 暴露后明显升高。组织因子（TF）和凝血因子 FXa 增加，而 vWF 则因 PM 而显著降低。凝血酶-抗凝血酶复合物（TAT）和纤维蛋白溶解因子（t-PA）升高，而抗凝因子（TFPI 和 AT-III）的表达无明显变化。为了阐明 PM 与 DIC 的关系，我们检查了 DIC 的一般诊断指标：PM 延长 PT 并增加 D-二聚体的表达，但降低血小板计数和纤维蛋白原。此外，JAK1 和 STAT3 的基因水平呈上升趋势，而 JAK2 的表达几乎没有影响。并且 PM 处理大鼠血管中的炎性因子（IL-6、IL-1β 和 TNF）表达上调。总之，我们的结果发现 PM 可诱导炎症反应、血管内皮损伤和促血栓形成状态，最终导致 DIC。这将为 PM 与心血管疾病之间的联系提供新的证据。
