本文選題：DEHP + 哮喘模型�。� 參考：《華中師范大學》2013年碩士論文

【摘要】：DEHP是目前使用最廣泛的一種增塑劑,因容易被釋放到環(huán)境中,所以成為一種常見的環(huán)境污染物。DEHP多種毒性和對人類健康危險的研究日益增多,近年來的研究發(fā)現(xiàn)DEHP與過敏性疾病存在一定關系,有研究證明室內塵埃中的DEHP含量與兒童哮喘以及哮喘樣癥狀的發(fā)生存在聯(lián)系。關于DEHP致哮喘作用分子機理的研究,多從傳統(tǒng)的Thl/Th2途徑展開。近年來,機體內有別于Thl和Th2的CD4+效應T細胞另一種Th17細胞被發(fā)現(xiàn),Th17細胞對炎癥反應的促進作用受到越來越多的關注。為探究Th17細胞在DEHP致小鼠哮喘的發(fā)病機制中的作用,本實驗在小鼠哮喘模型的基礎上,研究DEHP在有無OVA致敏的條件下,IL-17在小鼠相關組織中的變化。 雄性BalB/c小鼠隨機分為：未處理對照組、DEHP單獨染毒組、卵清蛋白致敏組、DEHP+OVA聯(lián)合染毒組,每組6只。哮喘模型通過OVA致敏加激發(fā)的方式建立。DEHP染毒組連續(xù)54d進行10mg/kg/day DEHP灌胃。OVA染毒組、DEHP+OVA染毒組在第54～59d進行1%OVA霧化(30min/day),誘發(fā)小鼠哮喘癥狀。第60d進行以下操作：血清制備,肺功能測試,肺泡灌洗液樣品收集和肺組織勻漿的制備。檢測的指標包括哮喘模型相關指標和肺組織中IL-17的檢測。結果表明,與OVA致敏組相比,DEHP+OVA聯(lián)合染毒組小鼠氣道高反應性顯著增強,肺部的病理變化也非常嚴重,肺泡灌洗液中嗜酸性粒細胞和中性粒細胞占白細胞總數(shù)的比例均增加,血清中T-IgE含量也顯著性增加；與對照組相比,DEHP染毒組小鼠肺組織勻漿和肺泡灌洗液中IL-17濃度均顯著性增加(p0.05),DEHP與OVA聯(lián)合染毒組小鼠BALF的IL-17則極顯著增加(p0.01)。表明DEHP對小鼠哮喘的誘導作用可能通過Th17細胞群介導。 綜合分析實驗結果發(fā)現(xiàn),DEHP能對哮喘發(fā)生產生影響,我們推斷：首先,DEHP+OVA聯(lián)合染毒組與OVA致敏組相比,血清中T-IgE極顯著增加,氣道高反應性上升,嗜酸性粒細胞比例增加,氣道重塑嚴重以及細胞炎癥因子濃度增加,可知DEHP參與了小鼠哮喘的發(fā)生過程,并通過類似免疫“佐劑”的作用加劇了小鼠哮喘癥狀。其次,IFN-γ/IL-4比值的下降,說明在此過程中Th1/Th2的平衡向Th2類細胞群平移,這與前人的研究結論一致。最后,DEHP染毒組,DEHP+OVA聯(lián)合染毒組小鼠肺組織和肺泡灌洗液中IL-17濃度增加,證明Th17類群細胞和Th2類群細胞一樣通過增加分化,促進炎癥作用,參與了哮喘發(fā)生的過程,表明Th1/Th2平衡是不完善的,DEHP促進炎癥發(fā)生的過程涉及Th1、Th2和Thl7三類細胞群。
[Abstract]:DEHP is one of the most widely used plasticizers at present. Because it is easy to be released into the environment, it has become a common environmental pollutant.Recent studies have found that there is a relationship between DEHP and allergic diseases. It has been proved that the content of DEHP in indoor dust is associated with the occurrence of asthma and asthmatic symptoms in children.The study on the molecular mechanism of asthma induced by DEHP is mainly based on the traditional Thl/Th2 pathway.In recent years, more and more attention has been paid to the role of Th 17 cells in promoting inflammation in T cells of CD4 effect, which are different from those in Thl and Th2.In order to investigate the role of Th17 cells in the pathogenesis of mouse asthma induced by DEHP, the changes of DEHP IL-17 in mice with or without OVA sensitization were studied on the basis of mouse asthma model.Male BalB/c mice were randomly divided into untreated control group (n = 6) and ovalbumin sensitized group (n = 6).The asthmatic model was established by OVA sensitization and stimulation. The rats in the .DEHP exposed group were treated with 10mg/kg/day DEHP for 54 days. The DEHP OVA group was treated with 1%OVA nebulization for 30 min / day on the 54th day and induced the asthmatic symptoms in the mice.On day 60, the following procedures were performed: serum preparation, lung function test, alveolar lavage fluid sample collection and lung tissue homogenate preparation.The indicators included asthma model and IL-17 in lung tissue.The results showed that compared with the OVA sensitized group, the airway hyperresponsiveness and the pathological changes of the lungs were significantly increased in the mice treated with OVA OVA, and the proportion of eosinophils and neutrophils in the alveolar lavage fluid to the total number of leukocytes was increased.Compared with the control group, the concentration of IL-17 in the lung tissue homogenate and alveolar lavage fluid of the control group was significantly higher than that of the control group, and the IL-17 of the BALF of the mice exposed to OVA was significantly higher than that of the control group.The results suggest that the induction of asthma by DEHP may be mediated by Th17 cell group.The results of comprehensive analysis showed that DEHP could affect the occurrence of asthma. We inferred that: first, compared with OVA sensitized group, the serum T-IgE level was significantly increased, airway hyperresponsiveness and eosinophilic granulocyte ratio were increased.Severe airway remodeling and increased concentration of cytokines suggest that DEHP is involved in the development of asthma in mice and exacerbates the symptoms of asthma in mice through immune adjuvant.Secondly, the decrease of IFN- 緯 / IL-4 ratio indicates that the balance of Th1/Th2 shifts to Th2 cell group in this process, which is consistent with previous studies.Finally, the concentration of IL-17 in lung tissue and alveolar lavage fluid of mice exposed to DEHP OVA combined with DEHP was increased, which proved that Th17 group cells and Th2 group cells increased differentiation, promoted inflammation and participated in the process of asthma.The results suggest that the Th1/Th2 balance is imperfect and the process of promoting inflammation involves Th1Th _ 2 and Thl7.
【學位授予單位】：華中師范大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R562.25;R-332

【參考文獻】

相關期刊論文 前10條

1 張娟;趙銘山;;Th17細胞的研究[J];濱州醫(yī)學院學報;2010年05期

2 吳平谷,韓關根,王惠華,趙瑩;飲用水中鄰苯二甲酸酯類的調查[J];環(huán)境與健康雜志;1999年06期

3 林興桃;沈婷;禹曉磊;王小逸;;室內降塵中鄰苯二甲酸酯污染特征分析[J];環(huán)境與健康雜志;2009年12期

4 熊鵬翔;龔嫻;鄧磊;;南昌市農田土壤和水樣中鄰苯二甲酸酯污染物的分析[J];化學通報;2008年08期

5 焦飛,多克辛,王玲玲,申劍,彭華,朱敘超,戎征;河南省主要城市水源水中微量有毒有害有機污染現(xiàn)狀調查與研究[J];中國環(huán)境監(jiān)測;2004年02期

6 王立鑫;趙彬;劉聰;林輝;張寅平;;室內鄰苯二甲酸酯(PAEs)暴露量分析[J];建筑科學;2010年06期

7 關卉;王金生;萬洪富;李丕學;楊國義;;雷州半島典型區(qū)域土壤鄰苯二甲酸酯(PAEs)污染研究[J];農業(yè)環(huán)境科學學報;2007年02期

8 蔡全英,莫測輝,李云輝,曾巧云,王伯光,肖凱恩,李海芹,徐國生;廣州、深圳地區(qū)蔬菜生產基地土壤中鄰苯二甲酸酯(PAEs)研究[J];生態(tài)學報;2005年02期

9 王連平,羅南,張春獻;塑料食品袋溶出酞酸酯DBP與DEHP的測定[J];同濟大學學報(醫(yī)學版);2004年01期

10 葛海生;劉元瑞;汪杰;;氣相色譜法測定PVC輸液袋中DEHP的含量[J];武警醫(yī)學;2006年02期

，

本文編號：1744912