乏氧状态下HIF1α- Hilpda/FSP27介导的脂质储积在激素性股骨头坏死中的作用

项目名称： 乏氧状态下HIF1α- Hilpda/FSP27介导的脂质储积在激素性股骨头坏死中的作用

项目编号： No.81500669

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： 李航

作者单位： 中国人民解放军总医院

项目金额： 18万元

中文摘要： 激素性股骨头坏死（SNFH）早期病理表现为骨髓脂肪化，即骨髓内脂质储积（脂肪组织肥大和增生）；而缺血缺氧是其病程进展及加重的重要因素。目前SNFH发病机制仍不清，其中关于乏氧微环境与骨髓内脂质储积关系的研究较少。研究发现，肝细胞内低氧诱导因子（HIF1α）可激活其下游缺氧诱导脂滴蛋白（Hilpda）的表达，进而促进细胞内脂质储积。我们前期研究显示，SNFH的髓腔组织内Hilpda的表达水平明显升高，且与脂滴特异蛋白27（FSP27）存在相互作用。FSP27可促进脂肪细胞肥大和成脂分化。由此我们推测HIF1α-Hilpda/FSP27通路可能对SNFH骨髓脂肪化的进展发挥作用。本研究拟探索HIF1α-Hilpda/FSP27通路对细胞乏氧状态下脂质含量、脂滴大小、脂代谢及骨髓基质干细胞成脂分化的影响，进而阐明Hilpda与FSP27相互作用的位点、时相等机制，为SNFH防治提供新的思路。

中文关键词： 缺氧诱导因子1α（HIF1α）；乏氧诱导脂滴相关蛋白（Hilpda）；脂肪组织特异蛋白27（FSP27）；缺氧/乏氧；激素性股骨头坏死（SNFH）

英文摘要： Steroid-induced necrosis of the femoral head (SNFH) is characterized by hyperplasia and hypertrophy of adipose tissue in its early pathologic changes, and recognized to be induced or worsened under ischemia-hypoxia. However, the mechanism of SNFH is not clear and there is less study on hypoxia induced lipid accumulation in SNFH. Hypoxia-inducible lipid droplet-associated (Hilpda) is reported to be a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1α (HIF1α), and is involved in triglyceride storage in hepatocytes. Our earlier research proved that the expression of Hilpda increased significantly in fatty infiltration of the bone marrow in SNFH and Hilpda could interact with fat-specific protein of 27KD (FSP27), which played an important role in fusion of lipid droplets (hypertrophy of adipose tissue) and differentiation of adipocytes (hyperplasia of adipose tissue). We initiate the current study to explore the effect of HIF1α-Hilpda/FSP27 pathway on numbers and sizes of lipid droplet, synthesis and hydrolysis of triglycerides and adipic differentiation of bone marrow stromal stem cells (BMSC) under hypoxic condition. Further, we investigate the mechanism of the interaction of Hilpda and FSP27. This study may provide new thinking for the treatment of SNFH.

英文关键词： Hypoxia-inducible factor-1α;Hypoxia-inducible lipid droplet-associated;Fat-specific protein of 27KD;Hypoxia;Steroid-induced necrosis of the femoral head