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题名: POPs诱导动脉粥样硬化以及microRNA的调控作用
作者: 黄风尘
学位类别: 硕士
答辩日期: 2014
授予单位: 中国科学院研究生院
授予地点: 北京
导师: 杜宇国
关键词: POPs ; microRNA ; 动脉粥样硬化 ; 基因芯片
其他题名: Atherosclerosis Induced by POPs and the Regulation Role of MicroRNA
中文摘要:       持久性有机污染物(POPs)在环境中长久存在难以降解,可通过各种环境介质在生物体中富集,并具有广泛的毒性作用,如免疫毒性、神经毒性和生殖毒性等。此外,众多的流行病学研究表明POPs暴露与心血管疾病的发生发展在统计学上有相关性,但机理上尚不确定。microRNA(miRNA)能够负向调控mRNA的表达,在转录后水平上对mRNAs网络起重要的调控作用。本研究旨在探究POPs暴露对心血管疾病的影响,以及miRNA的调控作用。 本课题选择POPs中比较典型的两种污染物TCDD以及Aroclor1254为研究对象,暴露动脉粥样硬化的研究模型ApoE-/-小鼠。利用基因芯片的表达数据考察暴露后小鼠肝脏中与动脉粥样硬化发生相关的mRNA和miRNA的差异表达,结合IPA软件分析差异表达的miRNA和mRNA,揭示POPs暴露对基因调控网络和信号通路的影响。 本研究主要结果如下: 1. TCDD暴露后有22个差异表达的miRNA能够靶向调控1981个差异表达的mRNA。这些差异表达的mRNA和miRNA参与调控TCDD暴露后与糖、脂代谢相关的通路,如PPAR信号通路,胰岛素信号通路和WNT信号通路。我们的结果特别强调miRNA-27a,miRNA-15b和let-7i在TCDD暴露后糖、脂代谢相关通路中的调节作用。 2. Aroclor1254暴露后有18个差异表达的miRNA能够靶向调控110个差异表达的mRNA,二者可共同影响糖代谢、脂代谢、细胞死亡、分子运输等生物学功能。进一步考察与动脉粥样硬化发生发展密切相关的糖代谢、脂代谢调控网络,发现miRNA-22、let-7family、miRNA-15a/b,以及靶基因PPARα、PPARγ辅助激活因子1α和Foxo1,在PCBs暴露致动脉粥样硬化发生发展的糖脂代谢异常发挥了重要作用。
英文摘要:       Persistent Organic Pollutants(POPs) exist in environment for a long time, and could concentrate in the organism through a variety of environmental media. POPs have a wide range of toxic effects, like immune toxicity, neurotoxicity, reproductive toxicity and so on. Moreover, epidemiological studies have shown that POPs exposure and development of cardiovascular disease are in correlation statistically, but the mechanism is not well known. microRNA (miRNA) are powerful negative regulators of mRNA expression, and therefore, are responsible for the modulation of mRNA networks post-transcriptionally. This research aims to explore POPs exposure effect on cardiovascular disease and the regulation role of miRNA. This study chose two typical pollutants TCDD and Acroclor1254 as research object to exposure ApoE-/- mice, which were model animal in atherosclerosis. Expression data in microarray were used to study differentially expression miRNA and mRNA in mice liver related with atherosclerosis. This study explored POPs exposure effect on gene network and signaling pathway through analyzing differential expression of miRNA and mRNA by IPA software. The results were as follows: 1. 22 differential expressed miRNA could regulate 1981 differential expressed mRNA after TCDD exposure. These modulated miRNA and mRNA that appeared to participate in TCDD-responsive pathways relevant to lipid or sugar metabolism, such as PPAR Signaling pathway, Insulin Signaling pathway, WNT Signaling pathway. Our results particularly highlighted the potential of microRNA-27a, microRNA-15b and let-7i as novel players in specific pathways related with lipid and glucose metabolism after TCDD response. 2. 18 miRNA could regulate 110 mRNAs after Aroclor1254 exposure, both of them could modulate the common biological functions, such as glucose metabolism, lipid metabolism, cell death and survival and cell transport. Further investigation showed that miRNA-22, let-7 family, miRNA-15a/b and the target genes of PPARα, PPARγ-coactivator1α and Foxo1 played important roles on the metabolism of glucose and lipid, which were closely related with the development of atherosclerosis.
内容类型: 学位论文
URI标识: http://ir.rcees.ac.cn/handle/311016/35194
Appears in Collections:环境化学与生态毒理学国家重点实验室_学位论文

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Recommended Citation:
黄风尘. POPs诱导动脉粥样硬化以及microRNA的调控作用[D]. 北京. 中国科学院研究生院. 2014.
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