【摘要】：載脂蛋白M是載脂蛋白家族成員,主要存在于高密度脂蛋白(high-density lipoprotein, HDL)中,受到核受體、細(xì)胞因子等多種調(diào)節(jié)因素所調(diào)節(jié),并在高密度脂蛋白代謝中起著重要作用,與多種疾病關(guān)系密切。多種膽汁酸代謝過(guò)程中的關(guān)鍵核受體對(duì)載脂蛋白M(Apolipoprotein M, APOM)具有調(diào)節(jié)作用,本論文從膽汁酸代謝通路中重要的核受體——肝受體同系物-1(liver receptor homolog-1,LRH-1)入手,對(duì)APOM在膽汁酸代謝途徑中的作用進(jìn)行了初步研究。 論文的第一部分收集了阻塞性黃疸患者和正常對(duì)照組,利用ELISA夾心法對(duì)血漿中APOM的濃度進(jìn)行了測(cè)定,分析發(fā)現(xiàn)APOM不僅與脂代謝過(guò)程中的載脂蛋白A I (Apolipoprotein A I,APOA I)和脂蛋白(a)[lipoprotein(a), Lp(a)]之間存在顯著的正相關(guān)關(guān)系,而且與總膽汁酸(total bile acid, TBA)也存在顯著的正相關(guān)。提示APOM可能在膽汁酸代謝過(guò)程中起作用。 論文的第二部分通過(guò)過(guò)表達(dá)APOM基因和干擾APOM基因表達(dá)發(fā)現(xiàn)APOM的變化模式與LH1相一致。通過(guò)GW4064激活法尼酯X受體(farnesoid X receptor, FXR)后,使得LRH-1的表達(dá)被抑制,同時(shí)APOM的表達(dá)也被抑制,隨著處理時(shí)間的延長(zhǎng),這種抑制作用表現(xiàn)也越明顯,到24h時(shí)到達(dá)最低值,其后抑制作用逐漸減弱。提示LRH-1和APOM可能在膽汁酸代謝通路中發(fā)揮作用。 本論文所完成的APOM在阻塞性黃疸和正常人群中的對(duì)比分析以及在膽汁酸代謝通路中作用的初步探索,為研究APOM的轉(zhuǎn)錄調(diào)控機(jī)制及生理功能奠定了基礎(chǔ),有助于深入了解膽汁酸代謝的調(diào)控網(wǎng)絡(luò)。對(duì)闡明膽汁酸代謝系統(tǒng)疾病的發(fā)病機(jī)理,以及早期診斷、治療開辟新的途徑。
[Abstract]:Apolipoproteins M is a member of apolipoproteins family, which mainly exists in high density lipoprotein (high-density lipoprotein, HDL) and is regulated by nuclear receptors, cytokines and other regulatory factors, and plays an important role in high density lipoprotein metabolism. It is closely related to many diseases. Many key nuclear receptors in bile acid metabolism play an important role in regulating apolipoproteins M (Apolipoprotein M, APOM). In this paper, we start with 1 (liver receptor homolog-1,LRH-1, an important nuclear receptor in bile acid metabolism pathway. The role of APOM in bile acid metabolism was studied. In the first part of the paper, the patients with obstructive jaundice and the normal control group were collected. The concentration of APOM in plasma was determined by ELISA sandwich method. It was found that APOM was not only related to apolipoproteins A I (Apolipoprotein A I, in the process of lipid metabolism. There was a significant positive correlation between APOA I) and lipoprotein (a) [lipoprotein (a), Lp (a)], and also a significant positive correlation with total bile acid (total bile acid, TBA). It is suggested that APOM may play a role in bile acid metabolism. In the second part of the thesis, it was found that the change pattern of APOM was consistent with that of LH1 by overexpressing APOM gene and interfering with APOM gene expression. After activating farnesyl X receptor (farnesoid X receptor, FXR) by GW4064, the expression of LRH-1 and APOM were also suppressed. With the prolongation of treatment time, the inhibitory effect was more obvious and reached the lowest value at 24 h. After that, the inhibitory effect decreased gradually. It is suggested that LRH-1 and APOM may play a role in bile acid metabolism pathway. The comparative analysis of APOM in obstructive jaundice and normal population and the preliminary exploration of its role in bile acid metabolism pathway lay a foundation for the study of transcriptional regulation mechanism and physiological function of APOM. It is helpful to understand the regulatory network of bile acid metabolism. It opens up a new way to elucidate the pathogenesis, early diagnosis and treatment of bile acid metabolic system diseases.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R3411

【參考文獻(xiàn)】

中國(guó)期刊全文數(shù)據(jù)庫(kù) 前6條

1 胡敏;趙水平;張濤;潘藝;熊丹;;人載脂蛋白M的表達(dá)與純化[J];中南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2008年01期

2 胡志高;屈曉冰;胡敏;;載脂蛋白M與冠狀動(dòng)脈病變的關(guān)系[J];中國(guó)動(dòng)脈硬化雜志;2008年03期

3 黎照環(huán);胡敏;;人血清apo M的ELISA檢測(cè)方法評(píng)價(jià)[J];臨床檢驗(yàn)雜志;2011年03期

4 唐朝克,楊永宗;LXR和ABCA1對(duì)體內(nèi)膽固醇代謝的調(diào)節(jié)作用[J];生命的化學(xué);2003年05期

5 張艷;劉紅;彭家和;董金瑜;王強(qiáng);李良鵬;王永超;江渝;;激活類法尼醇X核內(nèi)受體(FXR)可下調(diào)載脂蛋白M在HepG2細(xì)胞中的表達(dá)[J];中國(guó)生物化學(xué)與分子生物學(xué)報(bào);2009年11期

6 潘藝;胡敏;湯立軍;;載脂蛋白M[J];生命的化學(xué);2012年06期

，

本文編號(hào)：2497206