高血压大鼠肾髓间质细胞脂滴的蛋白质组学和脂质组学研究

Renal medullary interstitial cells (RMICs) are characterized by numerous heterogeneous lipid droplets in the cytoplasm. They span the interstitial spaces between the loops of Henle and the vasa recta bundles. Previous studies demonstrated that these cells have the ability to synthesize a vasodepressor lipid called medullipin, with its chemical structure unknown. Thus far, the lipidomic and proteomic profile of lipid droplets of RMICs remain uncharacterized. Increasing evidence suggests that lipid droplets of RMICs may be the sources of a variety of vasoactive lipids including medullipin, which play important roles in the regulation of systemic blood pressure and local hemodynamics. The present study will compare the differences in lipidomic and proteomic profile of lipid droplets of RMICs between WKY and spontaneously hypertensive rat (SHR). Specific aim 1 aimed to build up the database of lipid droplet-associated proteins of RMICs in both WKY and SHR. Specific aim 2 will compare the lipid profiles of lipid droplets of RMICs between SHR and WKY rats, in searching for the potential vasodepressor substances. The completion of our study may help clarify the role of lipid droplets of RMICs in the pathogenesis of hypertension, which may shed light on the mechanism of essential hypertension and renal hypertension and provide potential therapeutic targets for the treatment of hypertension.

肾髓间质细胞(RMICs)中富含脂滴, 横向连接肾小管和直小血管, 并参与肾髓渗透压梯度的维持。研究表明RMICs可分泌一种具显著降压作用、但化学本质未明的中性脂质--髓脂素。目前，RMICs脂滴的脂组分及脂滴包被蛋白种类尚未阐明。我们推测RMICs的脂滴含有包括髓脂素在内的多种脂质活性物质，该细胞通过脂滴这一亚细胞器参与血压调节。本研究我们拟通过组学手段比较正常(WKY)与高血压大鼠(SHR)肾髓脂滴包被蛋白及其脂质组分的差异。研究内容一将在SHR和WKY大鼠RMICs中，用蛋白质组学方法获得其脂滴包被蛋白谱及异同；研究内容二将借助脂组学手段初步明确二者RMICs脂滴组分及其差异，为明确髓脂素的化学本质提供线索。本课题的开展将首次建立RMICs脂滴包被蛋白和脂质组分信息库，有助于阐明RMICs脂滴功能及在血压调节中的作用，从而为临床原发性和肾性高血压的发病机制提供可能解释及潜在治疗靶点。

研究表明肾髓间质细胞(RMICs)中富含脂滴可分泌一种具显著降压作用、但化学本质未明的中性脂质--髓脂素（medullipin）。目前，RMICs脂滴的脂组分及脂滴包被蛋白种类尚未阐明。我们围绕RMICs的脂滴中蛋白质、脂质与血压调节展开了研究。本研究我们通过组学手段比较正常(WKY)与高血压大鼠(SHR)肾髓脂滴包被蛋白及其脂质组分的差异。确认了：1）大鼠RMICs脂滴蛋白数据库；2）通过比较SHR和WKY大鼠RMICs蛋白质和脂质的差异，发现花生四烯酸和大麻素代谢通路的关键基因cyp4A14, FAAH, MAGL参与了RMICs脂滴对血压的调控，2-AG可能为脂滴内源性降血压物质。本课题的开展将首次建立RMICs脂滴包被蛋白和脂质组分信息库，为明确髓脂素的化学本质提供线索，有助于阐明RMICs脂滴功能及在血压调节中的作用，从而为临床原发性和肾性高血压的发病机制提供可能解释及潜在治疗靶点。