APOM在胆汁酸代谢LRH-1通路中作用的初步研究
发布时间：2019-06-11 12:59
【摘要】：载脂蛋白M是载脂蛋白家族成员,主要存在于高密度脂蛋白(high-density lipoprotein, HDL)中,受到核受体、细胞因子等多种调节因素所调节,并在高密度脂蛋白代谢中起着重要作用,与多种疾病关系密切。多种胆汁酸代谢过程中的关键核受体对载脂蛋白M(Apolipoprotein M, APOM)具有调节作用,本论文从胆汁酸代谢通路中重要的核受体——肝受体同系物-1(liver receptor homolog-1,LRH-1)入手,对APOM在胆汁酸代谢途径中的作用进行了初步研究。 论文的第一部分收集了阻塞性黄疸患者和正常对照组,利用ELISA夹心法对血浆中APOM的浓度进行了测定,分析发现APOM不仅与脂代谢过程中的载脂蛋白A I (Apolipoprotein A I,APOA I)和脂蛋白(a)[lipoprotein(a), Lp(a)]之间存在显著的正相关关系,而且与总胆汁酸(total bile acid, TBA)也存在显著的正相关。提示APOM可能在胆汁酸代谢过程中起作用。 论文的第二部分通过过表达APOM基因和干扰APOM基因表达发现APOM的变化模式与LH1相一致。通过GW4064激活法尼酯X受体(farnesoid X receptor, FXR)后,使得LRH-1的表达被抑制,同时APOM的表达也被抑制,随着处理时间的延长,这种抑制作用表现也越明显,到24h时到达最低值,其后抑制作用逐渐减弱。提示LRH-1和APOM可能在胆汁酸代谢通路中发挥作用。 本论文所完成的APOM在阻塞性黄疸和正常人群中的对比分析以及在胆汁酸代谢通路中作用的初步探索,为研究APOM的转录调控机制及生理功能奠定了基础,有助于深入了解胆汁酸代谢的调控网络。对阐明胆汁酸代谢系统疾病的发病机理,以及早期诊断、治疗开辟新的途径。
[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.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R3411
本文编号：2497206
[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.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R3411
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