【摘要】： 目的及意義維生素A(Vitamin A,VA)缺乏仍然是影響我國和發(fā)展中國家兒童健康的重要問題.VA營養(yǎng)對于維持粘膜屏障功能具有十分重要的作用,但是VA促進粘膜抗感染免疫功能的機制還有待于進一步闡明。本課題研究了VA營養(yǎng)狀態(tài)對粘膜樹突狀細胞(Dendritic Cell,DC)成熟分化和功能的影響,并探討了其對腸道粘膜抗感染免疫的調(diào)節(jié)作用. 方法通過建立VA缺乏大鼠模型并誘導(dǎo)腸道感染,應(yīng)用免疫組化、RT-熒光定量PCR、ELISA,觀察粘膜DC數(shù)目、成熟度、抗原識別受體表達水平、信號轉(zhuǎn)導(dǎo)以及對Th1/Th2細胞因子蛋白水平和基因轉(zhuǎn)錄水平的影響;并觀察視黃酸受體(RARs/RXRs)的表達變化. 結(jié)果VA缺乏與VA正常大鼠比較:1.腸粘膜DC的數(shù)目顯著增加,當合并感染時不僅DC數(shù)量而且成熟分化也明顯增加。2.腸集合淋巴小結(jié)中TLR2、TLR4的蛋白表達都明顯升高,在合并感染后TLR2的表達上調(diào)更明顯。3.主要由DC產(chǎn)生的細胞因子IL-12的表達顯著增高,伴有腸道感染時IL-12的產(chǎn)生進一步升高;Th1細胞因子IFN-γ和IL-2降低,感染后IFN-γ顯著降低;Th2細胞因子IL-10的產(chǎn)生明顯下降,在腸道感染時IL-4、IL-6和IL-10都顯著下降。4.腸道粘膜RARα、γ和RXRα、β、γ的表達都顯著降低,但在感染后這五種視黃酸受體亞型較VA缺乏未感染組顯著升高。 結(jié)論1.VA缺乏大鼠粘膜DC的增多和活化可能是誘導(dǎo)炎癥反應(yīng)增強,導(dǎo)致粘膜損傷的重要機制之一。2.腸粘膜Th1和Th2細胞因子的產(chǎn)生都顯著減少是VA缺乏大鼠粘膜免疫功能降低的重要特征之一。3.對細胞因子產(chǎn)生水平的調(diào)節(jié)可能是VAD影響粘膜免疫功能,加重粘膜感染損傷的重要機制。4。腸粘膜視黃酸受體的表達不僅與VA營養(yǎng)狀態(tài)呈正相關(guān)變化,而且可能還參與介導(dǎo)VA對粘膜抗感染免疫的調(diào)節(jié)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- 緯 and IL-2 decreased, and IFN- 緯 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 偽, 緯 and RXR 偽, 尾, 緯 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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R392

【參考文獻】

相關(guān)期刊論文 前10條

1 賀偉峰,吳軍,羅高興,易紹萱,黃赤兵,陳希煒,鄭峻松,馬兵,雷曉;大鼠樹突狀細胞的體外分離、純化、擴增及鑒定[J];第三軍醫(yī)大學(xué)學(xué)報;2002年08期

2 姚海麗,王衛(wèi)平,郭志平;維生素A對臍血淋巴細胞免疫功能的作用[J];中國兒童保健雜志;2002年06期

3 楊紅,王衛(wèi)平,楊毅,姚海麗;視黃酸受體在臍血淋巴細胞抗體生成中的作用[J];營養(yǎng)學(xué)報;2001年01期

4 周小建,王衛(wèi)平,楊毅;視黃酸對人胸腺細胞成熟分化影響及其作用機制[J];營養(yǎng)學(xué)報;2004年01期

5 魏東,楊毅,王衛(wèi)平;視黃酸對幼兒淋巴結(jié)B細胞發(fā)育的影響[J];營養(yǎng)學(xué)報;2004年06期

6 陶月紅;楊毅;王衛(wèi)平;;視黃酸對臍血樹突狀細胞的作用及其途徑[J];營養(yǎng)學(xué)報;2006年01期

7 王衛(wèi)平,楊毅,蘇貽新;人外周血淋巴細胞視黃酸受體基因的表達與調(diào)控[J];營養(yǎng)學(xué)報;1998年03期

8 楊紅,楊毅,王衛(wèi)平;視黃酸受體在臍血淋巴細胞細胞因子表達中的調(diào)節(jié)作用[J];中華兒科雜志;2001年11期

9 陶月紅,楊毅;維生素A對臍血樹突狀細胞分化與成熟及其功能的影響[J];中華兒科雜志;2004年05期

10 魏東,楊毅,王衛(wèi)平;視黃酸對小兒淋巴結(jié)B細胞發(fā)育的作用及其途徑[J];中華兒科雜志;2005年05期

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