發(fā)布時間：2018-05-20 18:12

  本文選題：柴油尾氣污染物 + 咳嗽高敏感性��； 參考：《廣州醫(yī)科大學(xué)》2017年碩士論文

【摘要】：機(jī)動車尾氣排放是我國大城市空氣污染的重要來源,PM2.5是重要的空氣污染物。在交通相關(guān)空氣污染物中,PM2.5主要來源于柴油機(jī)動車排放的廢氣。流行病學(xué)研究表明,交通相關(guān)空氣污染與咳嗽的患病率密切相關(guān)。研究證實(shí),迷走神經(jīng)/氣道的TRPA1能被柴油尾氣等空氣污染物激活,從而引起一系列呼吸道疾病。然而空氣污染物誘發(fā)咳嗽的機(jī)制尚未明確,空氣污染物與咳嗽敏感性的關(guān)系亦鮮有報道。本課題組前期進(jìn)行了室外的豚鼠暴露實(shí)驗(yàn),證實(shí)交通相關(guān)空氣污染能誘發(fā)豚鼠咳嗽敏感性增高。然而,室外暴露存在較多干擾因素,暴露環(huán)境不可控、不穩(wěn)定。因此,有必要構(gòu)建可控的、穩(wěn)定的室內(nèi)污染物暴露實(shí)驗(yàn),進(jìn)一步探討空氣污染物與咳嗽敏感性的關(guān)系。因而,本研究通過構(gòu)建可控的、穩(wěn)定的柴油尾氣室內(nèi)暴露環(huán)境,觀察柴油尾氣污染物與豚鼠咳嗽敏感性的關(guān)系,探討TRPA1在柴油尾氣污染物影響豚鼠咳嗽敏感性當(dāng)中的作用。目的構(gòu)建可控、穩(wěn)定的柴油尾氣室內(nèi)暴露誘導(dǎo)的豚鼠咳嗽高敏感模型并探討其機(jī)制。方法1、動物分組:分為對照組、低濃度尾氣暴露組、高濃度尾氣暴露組、低濃度尾氣暴露+HC-030031組、高濃度尾氣暴露+HC-030031組。2、構(gòu)建室內(nèi)暴露環(huán)境:暴露組豚鼠放置于柴油尾氣暴露室內(nèi)進(jìn)行暴露,每天3小時,連續(xù)14天。低濃度暴露組和低濃度尾氣暴露+HC-030031組以PM2.5濃度為200μg/m3作為目標(biāo)濃度,高濃度暴露組和高濃度尾氣暴露+HC-030031組以PM2.5濃度為1000μg/m3作為目標(biāo)濃度。對照組豚鼠飼養(yǎng)于相對潔凈的實(shí)驗(yàn)動物房。3、藥物干預(yù):低濃度尾氣暴露+HC-030031組和高濃度尾氣暴露+HC-030031組的每只豚鼠給予TRPA1特異性拮抗劑HC-030031(200mg/kg,ip)。每天給藥一次,于咳嗽激發(fā)前2h最后一次給藥。其余各組豚鼠不做任何給藥干預(yù)。4、咳嗽激發(fā)試驗(yàn)后12h處理動物,留取標(biāo)本,進(jìn)行BALF細(xì)胞總數(shù)計數(shù)和分類計數(shù)、肺組織形態(tài)學(xué)觀察、ELISA法檢測肺組織勻漿的P物質(zhì)含量、Western Blot法分別檢測迷走神經(jīng)節(jié)勻漿和肺組織勻漿的TRPA1含量。結(jié)果1、柴油尾氣暴露可使豚鼠的咳嗽潛伏期均縮短、咳嗽激發(fā)次數(shù)均增多,該效應(yīng)隨尾氣濃度的增高而愈發(fā)明顯。HC-030031可在一定程度上延長咳嗽潛伏期、減少咳嗽激發(fā)次數(shù)。2、柴油尾氣暴露后,BALF細(xì)胞總數(shù)增多,且隨尾氣濃度的增高而增多。柴油尾氣暴露可誘導(dǎo)豚鼠產(chǎn)生氣道炎癥,炎癥細(xì)胞以中性粒細(xì)胞和嗜酸性粒細(xì)胞為主,炎癥細(xì)胞比例隨尾氣濃度的增高而增高。HC-030031可使細(xì)胞總數(shù)、中性粒細(xì)胞和嗜酸性粒細(xì)胞比例下降。3、柴油尾氣暴露后,暴露組肺組織出現(xiàn)不同程度的血管/支氣管周圍炎、組織水腫和支氣管上皮脫落。HC-030031可在一定程度上抑制該效應(yīng)。4、柴油尾氣暴露后,肺組織SP含量增多,且隨暴露濃度的增高而增多;HC-030031可減少肺組織SP含量。5、柴油尾氣暴露后,肺組織、迷走神經(jīng)節(jié)的TRPA1含量均有不同程度的增多。兩個迷走神經(jīng)節(jié)中,TRPA1含量增多以頸靜脈神經(jīng)節(jié)為主。HC-030031可減少肺組織、迷走神經(jīng)節(jié)的TRPA1含量。結(jié)論:1、本實(shí)驗(yàn)構(gòu)建之柴油尾氣室內(nèi)暴露環(huán)境可誘導(dǎo)豚鼠咳嗽敏感性增高,產(chǎn)生氣道炎癥,該暴露方法可控、穩(wěn)定,可作為研究咳嗽高敏感性的一種動物模型。2、柴油尾氣污染物可誘導(dǎo)豚鼠產(chǎn)生非特異性氣道炎癥,以中性粒細(xì)胞和嗜酸性粒細(xì)胞增多為主,同時產(chǎn)生以P物質(zhì)增多的氣道神經(jīng)源性炎癥。3、柴油尾氣污染物可誘導(dǎo)豚鼠出現(xiàn)咳嗽高敏感性,與感覺神經(jīng)/氣道TRPA1的激活有關(guān)。
[Abstract]:Vehicle exhaust emission is an important source of air pollution in large cities in China. PM2.5 is an important air pollutant. In traffic related air pollutants, PM2.5 is mainly derived from exhaust emissions from diesel motor vehicles. Epidemiological studies have shown that traffic related air pollution is closely related to the incidence of coughing. Research has confirmed that vagus nerve / gas TRPA1 can be activated by air pollutants such as diesel exhaust, causing a series of respiratory diseases. However, the mechanism of air pollutants induced coughing is not yet clear, and the relationship between air pollutants and cough sensitivity is rarely reported. The cough sensitivity of guinea pigs increased. However, there were many disturbing factors in outdoor exposure, and the exposure environment was uncontrollable and unstable. Therefore, it is necessary to construct a controlled, stable indoor pollutant exposure experiment, and further explore the relationship between air pollutants and cough sensitivity. Therefore, this study is based on the construction of a controlled, stable diesel exhaust indoor storm. The relationship between the pollutants of diesel exhaust and the cough sensitivity of guinea pigs was observed, and the role of TRPA1 in the coughing sensitivity of the diesel exhaust in guinea pigs was investigated. Objective to construct a controllable and stable high sensitivity model of the guinea pig cough induced by diesel exhaust indoor exposure and explore its mechanism. Methods 1, the animals were divided into control group and low concentration group. The tail gas exposure group, the high concentration tail gas exposure group, the low concentration tail gas exposure +HC-030031 group, the high concentration tail gas exposing the +HC-030031 group.2 and the indoor exposure environment: the exposed group guinea pigs were exposed to the diesel exhaust exposure room for 3 hours a day for 14 days. The low concentration exposed group and the low concentration tail gas exposed +HC-030031 group were PM2.5 concentration. The target concentration was 200 mu g/m3, the high concentration exposure group and the high concentration tail gas exposed the +HC-030031 group with the concentration of PM2.5 1000 g/m3 as the target concentration. The guinea pigs in the control group were raised in the relatively clean laboratory animal room.3, and the drug intervention was given to each guinea pig in the low concentration tail gas exposure +HC-030031 group and the high concentration tail gas exposed group +HC-030031 group to TRPA1. The specific antagonist HC-030031 (200mg/kg, IP) was given once a day and the last dose of 2H before the cough was stimulated. The rest of the guinea pigs were not given any medication to interfere with.4. After the cough stimulation test, the animals were treated with 12h, and the specimens were collected, the total number of BALF cells was counted and classified, the lung histomorphology observation, and the ELISA method were used to detect P in the lung tissue homogenate. Western Blot method was used to detect the TRPA1 content of the vagus ganglion homogenate and lung homogenate. Results 1, the exposure of diesel exhaust could shorten the cough latency and increase the number of coughing times in guinea pigs. The effect was increased with the increase of tail gas concentration and.HC-030031 could extend the latent period of coughing to a certain extent and reduce the cough. After the emission of.2, the total number of BALF cells increased and increased with the increase of tail gas concentration. The exposure of diesel exhaust could induce airway inflammation in guinea pigs. The inflammatory cells were mainly neutrophils and eosinophils. The proportion of inflammatory cells increased with the increase of tail gas concentration and.HC-030031 could make the total number of cells and neutral particles fine. The proportion of cell and eosinophil decreased by.3. After the exposure of diesel exhaust, the lung tissues of the exposed group showed different degree of blood vessel / bronchi, tissue edema and bronchial epithelium shedding of.HC-030031 could inhibit the effect of.4 to a certain extent. After the diesel exhaust was exposed, the SP content of lung tissue increased, and increased with the increase of exposure concentration; HC-03 0031 could reduce the SP content of lung tissue.5. After the diesel exhaust was exposed, the TRPA1 content of the lung tissue and the vagus ganglion increased in varying degrees. In the two vagus ganglion nodes, the increase of the content of TRPA1 in the jugular ganglion based.HC-030031 could reduce the TRPA1 content of the lung tissue and the vagus nerve node. Conclusion: 1, the diesel exhaust indoor storm was constructed in this experiment. Exposure environment can induce increased cough sensitivity and airway inflammation in guinea pigs. The exposure method is controllable and stable. It can be used as an animal model.2 for the study of cough Gao Min. The diesel exhaust pollutants can induce nonspecific airway inflammation in guinea pigs, mainly with neutrophils and eosinophils, and the increase of P substance. The airway neurogenic inflammation.3, diesel exhaust pollutants can induce cough in guinea pigs, Gao Min sense, and the activation of sensory nerve / airway TRPA1.
【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R56

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本文編號：1915708