【摘要】：目的:研究維生素A(Vitamin A,VA)在新生期肺炎鏈球菌肺炎(streptococcus pneumoniae pneumonia,S.pp)誘導(dǎo)成年期哮喘發(fā)生中的作用。明確新生期S.pp促進(jìn)哮喘發(fā)生是否通過影響VA水平實(shí)現(xiàn)及感染后VA補(bǔ)充是否對哮喘發(fā)病具有抑制作用;方法:將SPF級BALB/c新生雌鼠(6-8天)隨機(jī)分為對照組(Con組)、肺炎鏈球菌肺炎組(S.pp組)及肺炎后VA補(bǔ)充組(S.pp+VA組),3周后(即生后4周)開始利用OVA致敏、激發(fā)建立OVA過敏性哮喘模型(OVA組、S.pp+OVA組及S.pp+VA+OVA組)。高效液相色譜法(HPLC)動態(tài)監(jiān)測新生期S.pp對小鼠血清、肝臟及肺組織中VA的影響,比較Con組、OVA組、S.pp+OVA組及S.pp+VA+OVA組小鼠肺組織病理改變、氣道高反應(yīng)性及肺組織炎癥細(xì)胞浸潤、CD4+T細(xì)胞亞群水平及支氣管肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中細(xì)胞因子差異,比較三組哮喘模型小鼠肺組織中STAT4總蛋白表達(dá)及磷酸化水平差異。結(jié)果:新生期S.pp引起肺部VA持續(xù)降低至感染后四周,新生期S.pp后補(bǔ)充VA可顯著降低哮喘模型肺組織炎癥細(xì)胞浸潤,減輕氣道高反應(yīng)性及氣道肺組織炎癥細(xì)胞浸潤,增加肺組織STAT4蛋白磷酸化水平,促進(jìn)Th1、Foxp3+Treg細(xì)胞表達(dá),抑制Th2細(xì)胞表達(dá),而對肺組織STAT4總蛋白表達(dá)及Th17細(xì)胞水平并無顯著影響。結(jié)論:VA抑制新生期S.pp誘導(dǎo)的哮喘發(fā)生,可能與VA影響STAT4蛋白活化,影響CD4+T細(xì)胞分化發(fā)育有關(guān)�？赡芡ㄟ^影響STAT4活化,影響CD4+T細(xì)胞分化發(fā)育而抑制S.pp誘導(dǎo)的哮喘發(fā)生。
[Abstract]:Objective: To study the role of Vitamin A (VA) in the occurrence of neonatal asthma induced by Streptococcus pneumoniae (S.p.) in neonatal period. In this study, the effects of S. pp in neonatal period on asthma were determined whether by influencing VA level and VA supplementation after infection. Methods: SPF BALB/ c newborn infants (6-8 days) were randomly divided into control group (Con group). After 3 weeks (i.e. 4 weeks after birth) of Streptococcus pneumoniae pneumonia group (S. pp.) and the post-pneumonia VA supplementation group (S. pp + VA group), an allergic asthma model was established (group A, S. pp + control group and S. pp + VA + treatment group). High performance liquid chromatography (HPLC) was used to dynamically monitor the effects of S. pp on VA in serum, liver and lung tissues of mice. The expression of STAT4 and the level of phosphorylation of STAT4 in lung tissues of mice with asthma were compared. Results: After neonatal period S. pp, pulmonary VA decreased continuously to four weeks after infection. The supplementation of VA after neonatal period S. pp could significantly reduce the infiltration of inflammatory cells in lung tissue of asthma model, reduce airway hyperresponsiveness and infiltration of inflammatory cells in lung tissue, increase the phosphorylation level of STAT4 protein in lung tissue, and promote Th1. Foxp3 + Treg cells express and inhibit the expression of Th2 cells, but there is no significant effect on the expression of STAT4 total protein and the level of Th17 cells in lung tissue. Conclusion: VA inhibited the occurrence of S. pp induced asthma, which might affect the activation of STAT4 protein and affect the differentiation and development of CD4 + T cells. It is possible to suppress the occurrence of S. pp-induced asthma by influencing the activation of STAT4, which affects the differentiation and development of CD4 + T cells.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R722.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 楊婷;羅征秀;符州;劉昌林;王莉佳;羅健;劉恩梅;;新生期小鼠非致死性肺炎鏈球菌感染模型的建立[J];中國生物制品學(xué)雜志;2012年07期

，

本文編號：2281103