具有抗氧化生物活性的植物化学物质介导胆固醇外流调节胆固醇代谢的分子机制备受关注，食源性多肽介导胆固醇外流的研究尚未见报道。本项目拟以固相合成的、具有降胆固醇及抗氧化活性的米糠多肽为对象，围绕ABCA1介导的胆固醇外流这一代谢途径，以载脂蛋白ApoA-I的氧化修饰和PPARγ-LXRα-ABCA1信号转导通路为切入点，阐明米糠多肽介导胆固醇外流的分子机制。通过巨噬细胞内胆固醇外流的静态表征和胆固醇逆转运的动态表征，揭示米糠多肽介导胆固醇外流的代谢过程；分析机体内组织器官的氧化状态， 探究米糠多肽在机体内的抗氧化应激活性；通过分析内源性抗氧化酶、ABCA1及其相关基因的mRNA及蛋白质表达水平，深刻阐明米糠多肽通过提升内源性抗氧化酶的表达调节ApoA-I的氧化修饰和PPARγ-LXRα-ABCA1信号转导通路的分子机制。研究结果将为进一步阐明食源性多肽的降胆固醇机制提供新的理论支持。

Phytochemicals with antioxidant actives mediating cholesterol efflux is another mechanism for cholesterol metabolism. To our knowledge, there were no reports about the cholesterol efflux mediating ability of peptides from food scours. The objective of the project is to investigate the effects of rice bran peptides on the cholesterol efflux pathway medicated by the ATP binding cassette transporter A1 (ABCA1). The oxidative modification of apolipoprotein A-I (ApoA-I) and the pathway of peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα), and ABCA1 will be focused on. Cholesterol efflux in macrophage cell line and reverse cholesterol transport in mice will be investigated to demonstrate the efflux mediating ability of rice bran peptides. Meanwhile, the antioxidant activities of rice bran peptides will be studied by analyzing the oxidation state of live and plasma. Furthermore, the mRNA and protein expression levels of antioxidant enzymes, ABCA1 and other related genes will be studied. The molecular mechanism of rice bran peptides medicating the oxidative modification of ApoA-I and the pathway of PPARγ- PPARγ- PPARγ will be explored, which may be related to the up-regulating of antioxidant enzymes expression by rice bran peptides. The research result will present an important theoretical support for the cholesterol lowering mechanism of peptides.