柴油机尾气吸入式暴露诱导小鼠肺动脉高压的机制研究

发布时间：2018-05-07 04:15

本文选题：空气污染 + 柴油机尾气　；参考：《浙江大学》2017年硕士论文

【摘要】：空气污染在当今的发展中国家已经成为一个日益严重的问题,近年来覆盖大部分中国的雾霾现象引起了公众的广泛关注,已有研究表明空气污染与心血管疾病的发生息息相关。肺动脉高压是致死率最高的心血管疾病之一,它会导致右心室衰竭甚至死亡。柴油机尾气是城市空气污染尤其是颗粒物的主要来源之一。目前,关于柴油机尾气吸入对于肺动脉高压影响的研究十分有限。因此,有必要开展柴油机尾气对肺动脉高压的动物实验研究。本研究建立了柴油机尾气吸入式暴露体系,生物暴露箱内以40L/min的流速通入经过过滤空气稀释的柴油机尾气,控制生物暴露箱内总悬浮颗粒物浓度为345±33.78μg/m3,NO 浓度为 236.67±22.75μg/m3,NO2 浓度为 350±30.80μg/m3,CO浓度为11.67±1.71mg/m3,SO2浓度为14.33±1.15μg/m3。将成年雄性ICR小鼠置于生物暴露箱内进行吸入式暴露,并检测小鼠右心室收缩压,右心室壁、肺动脉形态变化,血管平滑肌细胞增殖,血管内皮细胞的凋亡以及相关免疫因子的变化情况。在本研究中,我们发现柴油机尾气吸入会引起小鼠体内肺动脉高压症状的产生,例如伴随着右心室收缩压上升,右心室壁增厚以及肺部动脉血管的增厚。柴油机尾气暴露引起血管平滑肌增生以及肺部血管内皮细胞的凋亡。柴油机尾气吸入式暴露还会引起CD45淋巴因子的积累以及CD68巨噬细胞因子在肺部小动脉周围的聚集以及渗透。在进行柴油机尾气暴露之后,小鼠肺组织内由Th17细胞以及Th2细胞产生的促炎症细胞因子例如肿瘤坏死因子α、白介素-6以及白介素-13含量会有显著性的提升。本研究表明,柴油机尾气的暴露会通过诱导由多种促炎症的细胞因子特别是肿瘤坏死因子α、白介素-6以及白介素-13的多功能性积累所导致血管平滑肌细胞增殖以及内皮细胞凋亡,最终引起肺动脉高压。综上所述,本研究发现,柴油机尾气对肺动脉高压的发生起着无法轻忽的作用。考虑到当今社会空气污染越来越严重的情况及其对于人类健康的严重负面影响,了解柴油机尾气暴露对肺动脉高压等血管重塑相关疾病的影响及相关机制,对于阻断空气污染诱发该类疾病的防控存在重要意义。
[Abstract]:Air pollution has become an increasingly serious problem in today's developing countries. In recent years, the haze covering most of China has caused widespread public concern. Research has shown that air pollution is closely related to the occurrence of cardiovascular diseases. Pulmonary arterial pressure is one of the most fatal cardiovascular diseases, which will lead to the right. Diesel exhaust is one of the main sources of urban air pollution, especially particulate matter. At present, the research on the effect of diesel engine exhaust inhalation on pulmonary hypertension is very limited. Therefore, it is necessary to carry out the study of the diesel engine tail gas for the pulmonary hypertension. In the exposure system, the concentration of the total suspended particulate matter in the biological exposure box is 345 + 33.78 mu g/m3, the concentration of NO is 236.67 + 22.75 mu g/m3, the concentration of NO2 is 350 + 30.80 u g/m3, the concentration of CO is 11.67 + 1.71mg/m3, and the SO2 concentration is 14.33 + 1.15 micron g/m3., and the concentration of the total suspended particulate matter in the biological exposure box is controlled by the flow velocity of the filtered air. Adult male ICR mice were exposed to inhaled exposure in a biological exposure box, and the right ventricular systolic pressure, right ventricular wall, pulmonary artery morphology, vascular smooth muscle cell proliferation, vascular endothelial cell apoptosis and related immune factors were detected. In this study, we found that diesel engine exhaust inhalation will cause the mice body. The emergence of the symptoms of internal pulmonary arterial hypertension, such as the rise of the right ventricular systolic pressure, the thickening of the right ventricular wall, and the thickening of the pulmonary artery vessels. The exhaust exposure of the diesel engine causes vascular smooth muscle proliferation and the apoptosis of the pulmonary vascular endothelial cells. The diesel exhaust inhalation exposure will also cause the accumulation of CD45 lymphatic factors and the CD68 macrophage. The accumulation and infiltration of cytokines around the pulmonary arteries. After exposure to diesel exhaust, the levels of proinflammatory cytokines such as tumor necrosis factor alpha, interleukins -6 and interleukin -13 produced by Th17 cells and Th2 cells in the lung tissue of mice are significantly elevated. This study shows that the exhaust exposure of diesel engines is exposed. The proliferation of vascular smooth muscle cells and apoptosis of endothelial cells induced by the multifunction accumulation of various cytokines, especially tumor necrosis factor alpha (TNF), il--6 and interleukin -13, will lead to pulmonary arterial hypertension. Taking into account the increasingly serious situation of air pollution in today's society and its serious negative effects on human health, it is of great significance to understand the effect of diesel exhaust exposure on vascular remodeling related diseases, such as pulmonary arterial hypertension, and related mechanisms, to prevent the prevention and control of such diseases by blocking air pollution.

【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：X734.2;X503.22

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