本文關(guān)鍵詞： PM2.5 Smad RORγt FoxP3 SB431542　出處：《新疆醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:探討PM2.5細(xì)顆粒物對(duì)大鼠肺組織損傷的分子免疫作用機(jī)制。方法:(1)觀察大氣細(xì)顆粒物PM2.5對(duì)大鼠肺部組織造成的病理學(xué)改變,并篩選出最適宜染毒劑量。(2)收集肺泡灌洗液進(jìn)行白細(xì)胞分類及計(jì)數(shù)。取右肺組織病理學(xué)檢查,熒光定量PCR法檢測TGF-β1、Smad2/3、RORγt、Foxp3 mRNA水平的變化,同時(shí)對(duì)Smad2、RORγt、FoxP3 mRNA水平與血清中IL-6、IL-17a、TGF-β1表達(dá)的相關(guān)性進(jìn)行分析。結(jié)果:(1)肺組織HE病理學(xué)改變:Ctrl、sham組肺泡腔大小均勻,肺泡壁完整,部分區(qū)域有少量出血及炎性細(xì)胞浸潤;L、M、H組大鼠肺組織肺間隔增寬,同時(shí)見大量炎性細(xì)胞浸潤,并隨著劑量增加組織損傷加重,H組肺膿腫形成,炎性細(xì)胞崩解壞死。(2)ELISA檢測顯示Ctrl、sham、SB431542組之間血清IL-6、IL-17a、TGF-β1水平差異無統(tǒng)計(jì)學(xué)意義(P0.05);與Ctrl、sham、SB431542組相比,PM2.5組血清IL-6、IL-17a、TGF-β1水平增高(P0.05)。(3)Ctrl及sham組肺泡灌洗液中中性粒細(xì)胞、嗜酸性粒細(xì)胞、淋巴細(xì)胞和巨噬細(xì)胞計(jì)數(shù)差異無統(tǒng)計(jì)學(xué)意義(P0.05);與sham組相比,PM2.5組中性粒細(xì)胞、嗜酸性粒細(xì)胞、淋巴細(xì)胞均升高(P0.05),巨噬細(xì)胞計(jì)數(shù)降低(P0.05);與PM2.5組相比,SB431542組中性粒細(xì)胞、嗜酸性粒細(xì)胞、淋巴細(xì)胞降低(P0.05),巨噬細(xì)胞計(jì)數(shù)升高(P0.05)。(4)肺組織病理:Ctrl及sham組肺泡大小均勻,肺泡壁完整;PM2.5組肺組織內(nèi)見大量炎性細(xì)胞浸潤,肺間隔增寬;SB431542組肺組織損傷程度減輕,少量炎性細(xì)胞浸潤。(5)Ctrl、sham組和SB431542組之間Smad2、TGF-β1、RORγt、Foxp3 mRNA水平差異無統(tǒng)計(jì)學(xué)意義(P0.05);與Ctrl、sham組和SB431542相比,PM2.5組Smad2、TGF-β1、RORγt、Foxp3 mRNA水平均增高(P0.05)。(6)相關(guān)性分析:肺組織Smad2 mRNA含量與血清中IL-6、IL-17a和TGF-β1成正相關(guān),相關(guān)系數(shù)分別為(r=0.817,r=0.826,r=0.862,P0.05);RORγt mRNA水平與血清IL-6、IL-17a、TGF-β1表達(dá)呈正相關(guān),相關(guān)系數(shù)分別為(r=0.890,r=0.823,r=0.818,P0.05);Foxp3 mRNA水平與血清IL-6、IL-17a、TGF-β1表達(dá)呈正相關(guān),相關(guān)系數(shù)分別為(r=0.912,r=0.812,r=0.846,P0.05)。結(jié)論:大氣細(xì)顆粒物PM2.5能夠引起大鼠肺組織損傷,其損傷程度隨染毒劑量的增加而加重。其可能的主要機(jī)制是TGF-β1表達(dá)增強(qiáng),刺激肺部Smad2、RORγt和Fox P3表達(dá),激發(fā)機(jī)體的免疫反應(yīng),使得血液中促炎性細(xì)胞因子IL-6、IL-17a、TGF-β1增多,從而導(dǎo)致組織的免疫炎性損傷。
[Abstract]:Objective: to investigate the molecular immunological mechanism of lung injury induced by fine particles of PM2.5 in rats. Methods: the pathological changes of lung tissue induced by PM2.5 were observed. The most suitable dose was selected to collect the alveolar lavage fluid for leukocyte classification and count. The right lung histopathology was used to detect the level of TGF- 尾 1 Smad2 / 3 ROR 緯 tFoxp3 mRNA. At the same time, the correlation between the level of FoxP3 mRNA and the expression of IL-6 / IL-17a- 尾 _ 1 in serum was analyzed. Results: the pathological changes of lung tissue were as follows: the size of alveolar cavity was uniform and the alveolar wall was intact. A small amount of hemorrhage and inflammatory cell infiltration were observed in some areas. The pulmonary septum was enlarged and a large number of inflammatory cells were infiltrated in the lung tissue of the rats in the LG-MU H group, and the pulmonary abscess was formed with the increase of the dose of the tissue injury in the H group. The results of Elisa showed that there was no significant difference in serum levels of IL-6, IL-17a1 and TGF- 尾 1 between the two groups, but the levels of IL-6 and IL-17a TGF- 尾 1 in PM2.5 group were significantly higher than those in Ctrlsb 43 1542 group, and the levels of neutrophils, eosinophils, eosinophils in alveolar lavage fluid of sham group were higher than those in PM2.5 group. Compared with sham group, neutrophil, eosinophil and lymphocyte in PM2.5 group increased P0.05, macrophage count decreased P0.05G, compared with PM2.5 group, neutrophil, eosinophil in SB431542 group, eosinophilic granulocyte, neutrophil, eosinophilic granulocyte, neutrophil, eosinophilic granulocyte, and eosinophilic granulocyte in PM2.5 group. The alveolar size of lung tissue was uniform in the group of lung pathology: the alveolar size was uniform, the alveolar wall was intact and PM2.5 group had a large number of inflammatory cells infiltration, and the injury degree of lung tissue was reduced in group SB431542. There was no significant difference in the levels of Smad2TGF- 尾 1 TGF- 尾 1tFoxp3 mRNA between the Smad2TGF- 尾 1 TGF- 尾 1 and SB431542 groups, but there was a positive correlation between the levels of Smad2TGF- 尾 1 TGF- 尾 1 Foxp3 mRNA and the serum levels of IL-6mil IL-17a and TGF- 尾 1 in the lung tissue compared with those in the Ctrlsham group and SB431542 group. There was a positive correlation between the level of ROR 緯 t mRNA and the expression of TGF- 尾 1 in serum IL-6, IL-17a- 尾 1, respectively. The correlation coefficient was that the level of Foxp3 mRNA was positively correlated with the expression of IL-6IL-17a- 尾 1 in serum. Conclusion: the level of PM2.5 can cause lung tissue injury in rats. The possible mechanism is that the expression of TGF- 尾 1 is increased, the expression of Smad2T ROR 緯 t and Fox P3 is stimulated, the immune response of the body is stimulated, and the pro-inflammatory cytokine IL-6, IL-17a- 尾 1 in the blood is increased. This leads to the immune inflammatory injury of the tissue.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R563;X513
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本文編號(hào)：1548834