本文選題：吲哚胺2 + 3-雙加氧酶　； 參考：《天津醫(yī)科大學(xué)》2015年碩士論文

【摘要】：本文旨在研究吲哚胺2,3-雙加氧酶(IDO)抑制小鼠小腸移植排斥反應(yīng)的作用機(jī)制。通過合成攜帶IDO序列的載體轉(zhuǎn)染獲得高表達(dá)IDO的小鼠樹突狀細(xì)胞(IDO+DC),結(jié)合色氨酸下游產(chǎn)物3-羥基鄰氨基苯甲酸(3-HAA),作用于體外受體來源的T細(xì)胞及小鼠小腸移植模型,探索IDO抑制小鼠小腸移植免疫反應(yīng)的具體原理和機(jī)制。目的：研究IDO+DC和3-HAA的抑制小鼠小腸移植排斥作用的機(jī)制。方法：DC用含IDO序列的腺病毒載體轉(zhuǎn)染,獲得高表達(dá)IDO的樹突狀細(xì)胞。獲取受體脾CD4+T淋巴細(xì)胞,分別與供體DC、DC+3-HAA、IDO+DC和IDO+DC+3-HAA進(jìn)行混合培養(yǎng),使用MTS、FCM以及ELISA等方法,全面檢測T淋巴細(xì)胞的增殖、凋亡、向Treg轉(zhuǎn)化及細(xì)胞因子環(huán)境變化情況。將IDO+DC及3-HAA輸注小腸移植受體小鼠(Balb\c),比較各組小鼠生存時(shí)間、抑制小腸組織情況、脾臟Treg亞群、血液細(xì)胞因子變化。結(jié)果：細(xì)胞實(shí)驗(yàn)中IDO+DC口3-HAA使T淋巴細(xì)胞的增殖受明顯抑制而凋亡增加,Treg亞群上調(diào),混合培養(yǎng)體系內(nèi)IFN-γ, TGF-β,IL-2口IL-10較空白對照組增加。動(dòng)物實(shí)驗(yàn)中,IDO+DC及3-HAA均能增加移植小鼠生存時(shí)間、減輕移植小腸組織損傷、上調(diào)Treg亞群,且二者效應(yīng)有疊加作用。結(jié)論：聯(lián)合應(yīng)用IDO+DC及3-HAA合用和單獨(dú)給予其中一種干預(yù)因素相比,對T細(xì)胞功能擁有更強(qiáng)的抑制效應(yīng)。IDO通過色氨酸代謝與色氨酸產(chǎn)物積累,直接途徑抑制T淋巴細(xì)胞增殖、誘導(dǎo)T淋巴細(xì)胞凋亡,間接途徑誘導(dǎo)Treg產(chǎn)生,共同抑制小鼠小腸抑制排斥反應(yīng)。
[Abstract]:The aim of this study was to investigate the mechanism of indoleamine 2o 3-dioxygenase (IDO) inhibiting rejection of small bowel transplantation in mice. Mouse dendritic cells (IDO DC) with high expression of IDO were obtained by synthesizing the vector carrying IDO sequence and binding 3-hydroxyo-aminobenzoic acid (3-HAA), a downstream product of tryptophan, to act on receptor derived T cells in vitro and small intestine transplantation model in mice. Objective: to explore the mechanism and mechanism of IDO inhibiting immune response of small bowel transplantation in mice. Aim: to study the mechanism of IDO DC and 3-HAA inhibiting the rejection of small bowel transplantation in mice. Methods dendritic cells with high expression of IDO were obtained by transfection with adenovirus vector containing IDO sequence. The recipient spleen CD4 T lymphocytes were obtained and cultured with donor DC 3-HAAZIDO DC and IDO DC 3-HAA, respectively. The proliferation, apoptosis, Treg transformation and cytokine environmental changes of T lymphocytes were detected by MTS- FCM and Elisa. The survival time, inhibition of intestinal tissue, spleen Treg subsets and changes of blood cytokines were compared in IDO-DC and 3-HAA recipient mice (Balb\ c),). Results: in the cell experiment, the proliferation of T lymphocytes was significantly inhibited and apoptosis was increased by 3-HAA in IDO DC, and IFN- 緯 and TGF- 尾 IL-2 were increased in mixed culture system as compared with those in control group. In animal experiments, both IDO DC and 3-HAA could increase the survival time of transplanted mice, alleviate the injury of small intestine and up-regulate the Treg subsets, and the two effects were superimposed. Conclusion: the combination of IDO DC and 3-HAA has a stronger inhibitory effect on T cell function. IDO directly inhibits T lymphocyte proliferation through tryptophan metabolism and tryptophan product accumulation. T-lymphocyte apoptosis was induced, Treg production was induced by indirect pathway, and small intestinal rejection was inhibited in mice.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R656.7

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