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大气污染诱导缺血性中风发病率增加的分子机制研究

批准号20877050 学科分类经济发展与贸易 ( G0304 )
项目负责人杜为公 负责人职称 依托单位山西大学
资助金额0.00
万元
项目类别面上项目 研究期限2009 年 01 月 01 日 至
2011 年 12 月 31 日
中文主题词缺血性脑中风;大气污染;炎症反应;内皮功能障碍;中动脉线拴(MCAO)模型
英文主题词Ischemic stroke; Air pollution; Inflammation; Endothelial dysfunction; Middle cerebral artery occlusion (MCAO) model

摘要

中文摘要 流行病学研究表明,大气污染可诱导缺血性脑中风病死率显著增加,但其效应污染物还不清楚,相关分子机制更是鲜见报道。本项目考察了SO2,NO2和PM10暴露与大鼠缺血性脑中风发生发展的相关性及损伤发生的机制,结果表明:(1)SO2吸入诱导正常大鼠脑皮层缺血相关内皮和炎性因子表达浓度依赖性显著上调;低浓度暴露则加重中动脉线栓(MCAO)模型大鼠的内皮损伤和炎性反应,增加神经元凋亡数量和脑缺血局灶体积。(2)NO2吸入增加正常大鼠血液粘度,造成脑皮层缺血相关内皮和炎性因子表达浓度依赖性显著变化;低浓度暴露延迟MCAO模型大鼠再灌注过程缺血局灶区域及神经行为学恢复,加重内皮损伤和炎性反应。(3)冬季采暖期PM10气管注入造成大鼠脑皮层组织病理学异常,缺血相关内皮因子和炎性介质表达发生显著变化,且效应的发生与PM10样品中多环芳烃和重金属成分相关。(4)SO2,NO2和PM10复合暴露可引起缺血相关内皮和炎性因子的表达变化,加重MCAO模型大鼠损伤效应。通过本项目,阐明诱导缺血性脑中风发生的大气污染物及效应浓度,为大气污染控制奠定实验基础;确立损伤发生的分子机制,为其健康防护和临床治疗提供理论依据。
英文摘要 Epidemiological studies indicate that air pollution significantly enhanced the incidence and death rate of stroke, especially ischemic stroke. However, the effective pollutants are unclear, and related molecular mechanisms are scantly reported. In the present study, we investigated the possibility for SO2, NO2 and PM10-induced ischemic stroke, and probed its molecular mechanisms. The results indicate that: (1) SO2 inhalation elevated the expression of endothelial and inflammatory markers (ET-1, COX-2, iNOS and ICAM-1) in rat cortex in a concentration-dependent manner. Interestingly, SO2 exposure at low concentration aggravated middle cerebral artery occlusion (MCAO)-induced endothelial dysfunction and inflammatory responses, increased neuronal apoptosis and cerebral infarct volume, and contributed to the development and progression of ischemic stroke in the brain. (2) NO2 inhalation concentration-dependently changed rat blood rheology, and increased the risk of ischemic injuries by changing the expression of endothelial (ET-1, eNOS and nNOS) and inflammatory markers (IL-1β, TNF-α, COX-2, iNOS and ICAM-1) in rat cortex. Especially, exposure to environmental NO2 exacerbated pathological injuries, delayed neurological structural and functional recovery from MCAO model rats, and the process involved in the endothelial dysfunction and inflammatory responses. (3) PM10 sample from heating season in winter induced mild pathological abnormal, followed by the changes of endothelial mediators (ET-1 and eNOS) and inflammatory markers (IL-1β, TNF-α, COX-2, iNOS and ICAM-1) in rat cortex. Also, the sample up-regulated bax/bcl-2 ratio and p53 expression, and induced neuronal apoptosis, which mimicked the injuries from cerebral ischemia and was associated with higher contents of PAHs and metals from coal burning in the sample. (4) Co-exposure to SO2, NO2 and PM10 changed the expression of endothelial and inflammatory biomarkers in rat cortex, and amplified the injuries of MCAO model rats. Our results reveal a mechanistic basis for exploring an association between typical air pollutants inhalation and increased risk for ischemic stroke, and opening up therapeutic approaches of treating, ameliorating, or preventing cerebral injuries resulting from SO2, NO2 and PM10 exposure in atmospheric polluting environment.
结题摘要 流行病学研究表明,大气污染可诱导缺血性脑中风病死率显著增加,但其效应污染物还不清楚,相关分子机制更是鲜见报道。本项目考察了SO2,NO2和PM10暴露与大鼠缺血性脑中风发生发展的相关性及损伤发生的机制,结果表明:(1)SO2吸入诱导正常大鼠脑皮层缺血相关内皮和炎性因子表达浓度依赖性显著上调;低浓度暴露则加重中动脉线栓(MCAO)模型大鼠的内皮损伤和炎性反应,增加神经元凋亡数量和脑缺血局灶体积。(2)NO2吸入增加正常大鼠血液粘度,造成脑皮层缺血相关内皮和炎性因子表达浓度依赖性显著变化;低浓度暴露延迟MCAO模型大鼠再灌注过程缺血局灶区域及神经行为学恢复,加重内皮损伤和炎性反应。(3)冬季采暖期PM10气管注入造成大鼠脑皮层组织病理学异常,缺血相关内皮因子和炎性介质表达发生显著变化,且效应的发生与PM10样品中多环芳烃和重金属成分相关。(4)SO2,NO2和PM10复合暴露可引起缺血相关内皮和炎性因子的表达变化,加重MCAO模型大鼠损伤效应。通过本项目,阐明诱导缺血性脑中风发生的大气污染物及效应浓度,为大气污染控制奠定实验基础;确立损伤发生的分子机制,为其健康防护和临床治疗提供理论依据。

成果

序号 标题 类型 作者
1 Assessing the phytotoxicity of different particle-size aged refuse using Zea mays L. bioassay 期刊 Sang Nan|Li Giangke|Niu Jing|
2 Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury 期刊 Sang Nan|Li Guangke|
3 SO2 inhalation induces protein oxidation, DNA-protein crosslinks and apoptosis in rat hippocampus 期刊 Yun Yang|Li Guangke|Sang Nan|Hou Li|
4 Landfill leachate affects metabolic responses of Zea mays L. seedlings 期刊 Sang Nan|Han Ming|Huang Mingzhu| Li Guangke|
5 Anandamide potentiation of miniature spontaneous excitatory synaptic transmission is mediated via IP3 pathway 期刊 Zhang Jian|Chen Chu|Sang Nan|

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