本文選題：甲醛 + FA誘導(dǎo)型哮喘�。� 參考：《華中師范大學(xué)》2008年碩士論文

【摘要】： 隨著人民生活水平的提高,室內(nèi)裝修已十分普遍,由此引起的裝修型室內(nèi)空氣污染問題日益嚴(yán)重,甲醛(Formaldehyde,FA)是裝修型室內(nèi)空氣污染的主要污染物之一。它具有污染時(shí)間長,來源范圍廣,污染水平高,生物毒性大等特點(diǎn)。室內(nèi)氣態(tài)FA的免疫毒性主要表現(xiàn)為免疫活性的增加,高濃度氣態(tài)FA可以誘發(fā)過敏性鼻炎和支氣管哮喘。特別是FA誘導(dǎo)型哮喘,發(fā)作嚴(yán)重時(shí)可以致人死亡,是室內(nèi)裝修型空氣污染造成的最嚴(yán)重的健康危害之一。對(duì)于FA誘導(dǎo)型哮喘的發(fā)病機(jī)理,傳統(tǒng)理論認(rèn)為FA是一種過敏原,通過特異性IgE途徑誘發(fā)哮喘,然而大量的流行病學(xué)調(diào)查在FA所致哮喘的患者體內(nèi)并未檢測到FA特異性IgE,提示我們FA可能有著不同于傳統(tǒng)的致病機(jī)理。Mendell于2007年在《indoor air》上發(fā)表綜述,認(rèn)為FA誘導(dǎo)性哮喘的機(jī)理研究主要集中在兩個(gè)方面,即FA對(duì)氣道的直接刺激作用和間接免疫作用。一方面,不同的動(dòng)物研究和人群研究結(jié)果表明,短期FA暴露即可引起受試者氣道反應(yīng)性的增加,表現(xiàn)為肺功能指數(shù)與空白組相比呈顯著上升趨勢。而另一方面,在相關(guān)動(dòng)物實(shí)驗(yàn)和流行病學(xué)調(diào)查研究中,FA的暴露可增加過敏原誘導(dǎo)型哮喘發(fā)病幾率及嚴(yán)重程度,顯示出FA在過敏原誘導(dǎo)型哮喘發(fā)病過程中的易化作用。然而在大多數(shù)研究中,FA的這兩種作用難以鑒別和區(qū)分�；贔A誘導(dǎo)型哮喘的相關(guān)機(jī)理研究,本實(shí)驗(yàn)旨在建立FA過敏原型哮喘大鼠職業(yè)模型,鑒別FA的兩種作用,為進(jìn)一步深入研究該疾病的分子機(jī)理奠定基礎(chǔ)。實(shí)驗(yàn)結(jié)果如下: 1.FA誘導(dǎo)型職業(yè)哮喘大鼠模型的建立 本研究采用SPF級(jí)Wistar大鼠,分別設(shè)立五個(gè)實(shí)驗(yàn)組:空白組、OVA致敏組、0.5 mg/m~3 FA+OVA組、3.0 mg/m~3 FA+OVA組和3.0 mg/m~3 FA單獨(dú)作用組,建立FA職業(yè)暴露模型。即采用FA職業(yè)暴露標(biāo)準(zhǔn),每天FA染毒6 h,染毒10 d,FA暴露期為各組實(shí)驗(yàn)大鼠進(jìn)行卵清白蛋白(Ovalbumin,OVA)致敏前10天。OVA霧化激發(fā)7天后進(jìn)行乙酰甲膽堿(O-Acetyl-β-methylcholine chloride,MCH)激發(fā)實(shí)驗(yàn)、肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)細(xì)胞計(jì)數(shù)、肺組織石蠟切片蘇木精伊紅(Hematoxylin and eosin,HE)染色、肺組織白細(xì)胞介素-4(Interleukin-4,IL-4)及干擾素-γ(Interferon-γ,IFN-γ)酶聯(lián)免疫反應(yīng)(Enzyme-Linked Immuno Sorbent Assay,ELISA)檢測實(shí)驗(yàn)。MCH激發(fā)實(shí)驗(yàn)及HE染色實(shí)驗(yàn)說明FA單獨(dú)作用組及FA-OVA聯(lián)合作用組均表現(xiàn)出了一種或幾種典型的哮喘樣癥狀,說明本研究成功建立了FA誘導(dǎo)型職業(yè)大鼠哮喘模型,為全面研究FA誘導(dǎo)型哮喘的分子機(jī)理奠定了堅(jiān)實(shí)的基礎(chǔ)。 2.FA直接作用和間接作用的鑒別 本實(shí)驗(yàn)通過FA單獨(dú)暴露模型和FA易化OVA哮喘大鼠模型的建立,對(duì)FA在FA誘導(dǎo)型哮喘發(fā)病過程中的直接作用和間接作用分別進(jìn)行了研究。結(jié)果表明0.5和3.0 mg/m~3的氣態(tài)FA暴露可顯著增加OVA致敏大鼠的氣道高反應(yīng)性、氣道結(jié)構(gòu)變化程度,同時(shí)顯著提高BALF中嗜酸粒細(xì)胞(Eosinophil,EOS)和白細(xì)胞總數(shù)以及肺組織中IL-4的表達(dá)水平,表明FA可能通過惡化EOS炎癥和促進(jìn)Th2類免疫反應(yīng)而易化或惡化OVA誘導(dǎo)型哮喘。對(duì)于3.0 mg/m~3 FA單獨(dú)作用組,一方面該組FA暴露可誘發(fā)實(shí)驗(yàn)大鼠持續(xù)的氣道高反應(yīng)性,伴隨著肺組織中IFN-γ表達(dá)水平的極顯著上升。另一方面該組實(shí)驗(yàn)大鼠氣道結(jié)構(gòu)、EOS計(jì)數(shù)均無顯著變化,而EOS占白細(xì)胞總數(shù)比例及肺組織中IL-4水平較空白組相比顯著下降,表明高濃度FA單獨(dú)暴露可能通過激活Th1類免疫反應(yīng)和非EOS炎癥而誘發(fā)AHR等哮喘樣癥狀。
[Abstract]:With the improvement of the living standard of the people, indoor decoration is very common, and the decoration type indoor air pollution is becoming more and more serious. Formaldehyde (Formaldehyde, FA) is one of the main pollutants in the decoration type indoor air pollution. It has the characteristics of long pollution time, wide source range, high pollution level, large biological toxicity and so on. Indoor gaseous FA The main immune toxicity is the increase of immune activity. High concentration of gaseous FA can induce allergic rhinitis and bronchial asthma. Especially, FA induced asthma can cause death when the attack is serious. It is one of the most serious health hazards caused by indoor air pollution. The traditional theory on the pathogenesis of FA induced asthma is the traditional theory. It is considered that FA is an allergens that induces asthma through a specific IgE pathway. However, a large number of epidemiological investigations have not detected FA specific IgE in patients with FA induced asthma, suggesting that FA may have different from the traditional pathogenicity mechanism,.Mendell in 2007, in , that the mechanism of FA induced asthma is considered. The study mainly focused on two aspects, the direct stimulation of the airway and the indirect immunization of the FA. On the one hand, the results of different animal studies and population studies showed that the short-term FA exposure could cause an increase in the airway responsiveness of the subjects, which showed a significant increase in the ratio of the pulmonary function index to the blank group. On the other hand, the related movement was related. In the experimental and epidemiological studies, FA exposure can increase the incidence and severity of allergen induced asthma, showing the susceptibility of FA in the pathogenesis of allergen induced asthma. However, in most studies, these two effects are difficult to identify and divide. Based on the mechanism of FA induced asthma, this is a study of the pathogenesis of asthma. The aim of the experiment was to establish the occupational model of FA allergic asthmatic rats, to identify the two effects of FA, and to lay the foundation for further study of the molecular mechanism of the disease. The experimental results are as follows:
Establishment of 1.FA induced model of occupational asthma in rats
In this study, SPF Wistar rats were used to establish five experimental groups: blank group, OVA sensitizing group, 0.5 mg/m~3 FA+OVA group, 3 mg/m~3 FA+OVA group and 3 mg/m~3 FA separate action group to establish a FA occupational exposure model. Valbumin, OVA) 10 days before.OVA atomization and excitation for 7 days, acetylmethacholine (O-Acetyl- beta -methylcholine chloride, MCH) excitation experiment, alveolar lavage fluid (Bronchoalveolar lavage fluid, BALF) cell count, lung tissue paraffin section hematoxylin eosin staining, lung tissue interleukin -4) and interferon gamma (Interferon- gamma, IFN- gamma) enzyme-linked immunosorbent assay (Enzyme-Linked Immuno Sorbent Assay, ELISA) test.MCH excitation experiment and HE staining experiment showed that FA individual action group and FA-OVA combined group showed one or several typical asthma like symptoms. The rat asthma model lays a solid foundation for the comprehensive study of the molecular mechanism of FA induced asthma.
Identification of direct and indirect effects of 2.FA
In this experiment, the direct and indirect effects of FA in the pathogenesis of FA induced asthma were studied by the FA exposure model and the model of FA susceptible OVA asthmatic rats. The results showed that the 0.5 and 3 mg/m~3 gaseous FA exposure could significantly increase the airway hyperresponsiveness and the degree of airway structure change in the OVA sensitized rats. A significant increase in the levels of Eosinophil, EOS, and the total number of leukocytes and the expression of IL-4 in the lung tissue in BALF indicates that FA may facilitate or exacerbate OVA induced asthma by worsening EOS inflammation and promoting Th2 immune responses. For 3 mg/m~3 FA alone, on the one hand, FA exposure can induce the continuous airway of experimental rats. Hyperresponsiveness was accompanied by a significant increase in the expression of IFN- gamma in lung tissue. On the other hand, there was no significant change in the airway structure and EOS count in the experimental rats, while the proportion of the total number of white cells and the level of IL-4 in the lung tissue were significantly lower than those in the blank group, indicating that the high concentration of FA may be activated by the activation of the Th1 immune response and not by the high concentration of FA. EOS inflammation induces asthma like symptoms such as AHR.
【學(xué)位授予單位】：華中師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R562.25;R-332

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