Department of Environment Health, School of Public Health, Fudan University, Shanghai, China.
Toxicol Lett. 2010 Mar 1;193(1):50-60. doi: 10.1016/j.toxlet.2009.12.002. Epub 2009 Dec 16.
The study is to explore the potential mechanisms linking fine particles and cardiovascular toxicity. Spontaneous hypertensive rats (SHR) and age-matched wistar kyoto (WKY) rats were exposed by intratracheal instillation to fine particles with the doses of 0.0, 1.6, 8.0 and 40.0mg/kg b.w., respectively. The exposure was conducted once a day, for three continuous days. Twenty-four hours after the last exposure, the rats were killed and the levels of high sensitive C-reactive proteins (hsCRPs), nitrous oxide (NO), D-dimer and endothelin-1 (ET-1) were measured in blood. Reverse transcriptase polymerase chain reaction (RT-PCR) assay assessed the expression of interleukin-1 beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), ET-1, Bax and Bcl-2 in left ventricle of rats. Meanwhile, cardiac histological lesions were assessed. The expression transforming growth factor-beta 1 (TGF-beta(1)) in left ventricle was measured by immunohistochemical staining. The results showed that the levels of hsCRP, D-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) increased in a dose-dependent manner, but NO and Bcl-2 decreased. Cardiac histology demonstrated exacerbated cardiac lesions in SHR when compared to WKY rats. Meanwhile, at the same dose exposed, the levels of hsCRP, d-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) were higher in SHR than those in WKY rats. The results indicated that ambient fine particles which entered into lungs could influence the cardiovascular system. When exposed to fine particles, SHR exhibited more severe cardiovascular injury in comparison to WKY rats. The results indicated that the inflammation, endothelial dysfunction, coagulation disorders and imbalance of apoptosis/anti-apoptosis might be the mechanisms of cardiovascular injury induced by fine particles. Different response between SHR and WKY rats after exposed to fine particles indicated that SHR was more susceptible than WKY rats to acute cardiac impairments from fine particle exposure.
这项研究旨在探索细颗粒物与心血管毒性之间的潜在关联机制。采用气管滴注法将不同剂量(0.0、1.6、8.0 和 40.0mg/kg.b.w.)的细颗粒物分别染毒自发性高血压大鼠(SHR)和同月龄的 Wistar 京都大鼠(WKY),每天染毒一次,连续染毒 3 天。末次染毒 24 小时后处死大鼠,检测血清中高敏 C 反应蛋白(hsCRP)、一氧化氮(NO)、D-二聚体和内皮素-1(ET-1)的含量,采用逆转录聚合酶链反应(RT-PCR)法检测大鼠左心室组织中白细胞介素-1β(IL-1β)、细胞间黏附分子-1(ICAM-1)、ET-1、Bax 和 Bcl-2 的表达水平,同时观察心脏组织病理学变化,并采用免疫组化法检测左心室组织中转化生长因子-β1(TGF-β1)的表达。结果显示,hsCRP、D-二聚体、ET-1 的水平以及 IL-1β、ICAM-1、ET-1、Bax 和 TGF-β1 的表达均呈剂量依赖性升高,而 NO 和 Bcl-2 的水平则逐渐降低。与 WKY 大鼠相比,SHR 大鼠的心脏组织病理学损伤更为严重。此外,在相同剂量染毒下,SHR 大鼠血清中 hsCRP、D-二聚体、ET-1 的水平以及左心室组织中 IL-1β、ICAM-1、ET-1、Bax 和 TGF-β1 的表达均高于 WKY 大鼠。这些结果表明,进入肺部的环境细颗粒物可影响心血管系统。与 WKY 大鼠相比,暴露于细颗粒物的 SHR 大鼠发生更严重的心血管损伤。由此推断,炎症、内皮功能障碍、凝血功能紊乱以及细胞凋亡/抗凋亡失衡可能是细颗粒物引起心血管损伤的机制。SHR 大鼠和 WKY 大鼠在暴露于细颗粒物后的不同反应表明,与 WKY 大鼠相比,SHR 大鼠对细颗粒物暴露引起的急性心脏损伤更为敏感。