糖皮质激素类药物通过调节miRNA诱导脂肪肝形成的作用研究

项目名称： 糖皮质激素类药物通过调节miRNA诱导脂肪肝形成的作用研究

项目编号： No.81503171

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘凤琼

作者单位： 福建医科大学

项目金额： 17.9万元

中文摘要： 糖皮质激素类药物的长期使用可增高机体糖皮质激素水平从而干扰正常脂质代谢而促进脂肪肝发生，而miRNA被报导参与了肝细胞脂质代谢的调节。我们已有的实验发现糖皮质激素类药物可以影响肝细胞某些miRNA的表达和诱导脂肪肝形成，而miRNA又与肝细胞的脂质代谢相关，提示miRNA在糖皮质激素类药物诱导的脂肪肝中发挥重要作用。本课题利用人肝癌HepG2细胞系、糖皮质激素类药物诱导的脂肪肝动物模型，应用miRNA芯片结合mRNA芯片法及miRNA 功能实验方法，拟研究：1）糖皮质激素类药物是否对miRNA存在广泛的调节作用，以及miRNA是否介导了糖皮质激素类药物诱导的脂肪肝形成；2）分析介导脂肪肝诱导作用的miRNA的分子靶点和调控的信号通路以及验证该“miRNA-靶基因信号通路是否参与糖皮质激素类药物对肝细胞脂质代谢的调控”。本研究将为糖皮质激素类药物临床副作用的防治提供新思路和途径。

中文关键词： 糖皮质激素；微小RNA；脂肪肝

英文摘要： Long-term glucocorticoid therapy can lead to elevated glucocorticoid level which interfer with lipid metabolism homeostasis leading to fatty liver. MicroRNA is a small non coding RNAs that primarily acts as sequence-specific inhibitors of messenger RNA (mRNA) translation. It has been widely reported that miRNA involves in lipid metabolism of hepatocytes. Our previous study revealed that glucocorticoid can affect miRNA levels and induce steatosis in hepatocytes, we also observed that certain miRNAs can down-regulate crucial genes in hepatic lipid metabolism, indicating that miRNA may plays important role in glucocorticoid induced fatty liver. In the present project, by using miRNA chip combined with mRNA chip and miRNA gain (loss) of function, we will explore whether or not glucocorticoid can affect miRNA expression and that if miRNA can mediate glucocorticoid induced fatty liver in HepG2 cell and glucocorticoid incuded fatty liver model. In further we will investigate the signal pathway through which miRNA induce steatosis and confirm that the signal pathway is involved in glucocorticoid induced steatosis and fatty liver. This study will provide new perspectives to attenuate a major side effects of glucocorticoid.

英文关键词： glucocorticoid;microRNA;fatty liver