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维生素A对肠道树突状细胞的影响与粘膜抗感染免疫的研究

发布时间:2019-01-11 15:04
【摘要】: 目的及意义维生素A(Vitamin A,VA)缺乏仍然是影响我国和发展中国家儿童健康的重要问题.VA营养对于维持粘膜屏障功能具有十分重要的作用,但是VA促进粘膜抗感染免疫功能的机制还有待于进一步阐明。本课题研究了VA营养状态对粘膜树突状细胞(Dendritic Cell,DC)成熟分化和功能的影响,并探讨了其对肠道粘膜抗感染免疫的调节作用. 方法通过建立VA缺乏大鼠模型并诱导肠道感染,应用免疫组化、RT-荧光定量PCR、ELISA,观察粘膜DC数目、成熟度、抗原识别受体表达水平、信号转导以及对Th1/Th2细胞因子蛋白水平和基因转录水平的影响;并观察视黄酸受体(RARs/RXRs)的表达变化. 结果VA缺乏与VA正常大鼠比较:1.肠粘膜DC的数目显著增加,当合并感染时不仅DC数量而且成熟分化也明显增加。2.肠集合淋巴小结中TLR2、TLR4的蛋白表达都明显升高,在合并感染后TLR2的表达上调更明显。3.主要由DC产生的细胞因子IL-12的表达显著增高,伴有肠道感染时IL-12的产生进一步升高;Th1细胞因子IFN-γ和IL-2降低,感染后IFN-γ显著降低;Th2细胞因子IL-10的产生明显下降,在肠道感染时IL-4、IL-6和IL-10都显著下降。4.肠道粘膜RARα、γ和RXRα、β、γ的表达都显著降低,但在感染后这五种视黄酸受体亚型较VA缺乏未感染组显著升高。 结论1.VA缺乏大鼠粘膜DC的增多和活化可能是诱导炎症反应增强,导致粘膜损伤的重要机制之一。2.肠粘膜Th1和Th2细胞因子的产生都显著减少是VA缺乏大鼠粘膜免疫功能降低的重要特征之一。3.对细胞因子产生水平的调节可能是VAD影响粘膜免疫功能,加重粘膜感染损伤的重要机制。4。肠粘膜视黄酸受体的表达不仅与VA营养状态呈正相关变化,而且可能还参与介导VA对粘膜抗感染免疫的调节作用。
[Abstract]:Objective and significance Vitamin A (Vitamin Ava) deficiency is still an important problem affecting the health of children in China and developing countries. VA nutrition plays a very important role in maintaining mucosal barrier function. However, the mechanism of VA promoting mucosal anti-infection immune function remains to be further elucidated. The purpose of this study was to investigate the effects of nutritional status of VA on the maturation, differentiation and function of mucosal dendritic cells (Dendritic Cell,DC), and to explore its role in the regulation of intestinal mucosal anti-infective immunity. Methods the rat model of VA deficiency was established and intestinal infection was induced. The number, maturity and expression of antigen recognition receptors were observed by immunohistochemistry and RT- fluorescence quantitative PCR,ELISA,. Signal transduction and its effect on Th1/Th2 cytokine protein level and gene transcription level; The expression of retinoic acid receptor (RARs/RXRs) was observed. Results VA deficiency was compared with normal VA rats: 1. The number of DC in intestinal mucosa increased significantly, and not only the number of DC but also the mature differentiation of intestinal mucosa increased significantly. 2. 2. The expression of TLR2,TLR4 protein in intestinal aggregate lymphoid nodules was significantly increased, and the expression of TLR2 was significantly increased after infection. The expression of IL-12, a cytokine produced mainly by DC, was significantly increased, and the production of IL-12 was further increased in patients with intestinal infection, while the expression of Th1 cytokines IFN- 纬 and IL-2 decreased, and IFN- 纬 decreased significantly after infection. The production of Th2 cytokine IL-10 decreased significantly, and IL-4,IL-6 and IL-10 decreased significantly in intestinal infection. 4. 5%. The expression of RAR 伪, 纬 and RXR 伪, 尾, 纬 in intestinal mucosa was significantly decreased, but the expression of these five retinoic acid receptor subtypes was significantly higher than that in VA deficient uninfected group after infection. Conclusion the increase and activation of mucosal DC in rats with 1.VA deficiency may be one of the important mechanisms that induce the enhancement of inflammatory response and mucosal injury. The decrease of Th1 and Th2 cytokines in intestinal mucosa is one of the important features of mucosal immune function reduction in VA deficient rats. The regulation of cytokine production may be an important mechanism of VAD affecting mucosal immune function and exacerbating mucosal infection. 4. The expression of retinoic acid receptor in intestinal mucosa was not only positively correlated with the nutritional status of VA, but also involved in the regulation of mucosal anti-infective immunity mediated by VA.
【学位授予单位】:复旦大学
【学位级别】:博士
【学位授予年份】:2008
【分类号】:R392

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