高静压下酶解甘薯肽抗血管紧张素II诱导的氧化应激作用机制

Hypertension shows serious harm on human health, angiotensin II-induced oxidative stress plays an important role in the pathogenesis of spontaneous hypertension, while bioactive peptides may provide new preventive and therapeutic ways of hypertension by anti-oxidative stress. Sweet potato protein is a potential active peptides source of plant protein sources. The peptides from sweet potato protein by enzymatic hydrolysis show certain antioxidant activity and antihypertensive effect, which activity can be significantly improved by hydrolysis under high hydrostatic pressure, but the mechanism is not well understood. In order to deeply understand the mechanism above, sweet potato protein is hydrolyzed under high hydrostatic pressure, and protein conformation change and its effects on enzymatic dynamics will be investigated in this study; The structure-activity relationship of sweet potato peptides by enzymatic hydrolysis under high hydrostatic pressure will be studied by analysis of peptide fragments release, primary structure and antioxidant activities; The molecular mechanism of sweet potato peptides with anti-angiotensin II-induced oxidative stress in vivo and in vitro will be clarified by evaluation of the signal transduction pathway (NF-κB and PI3K/AKT), thus providing a theoretical basis for the application of sweet potato peptides in functional health foods, and creating new ideas and programs in research and development of anti-oxidative stress peptides.

高血压严重危害人类健康，血管紧张素II诱导的氧化应激在其发病机制中发挥重要作用，而生物活性肽通过抗氧化应激可能提供防治高血压新途径。甘薯蛋白是植物源活性肽的潜在来源，甘薯酶解肽具有一定的抗氧化活性及降血压作用，而高静压下酶解能显著提高其活性，但作用机制尚不明确。为深入研究上述作用机制，本项目采用高静压下酶解甘薯蛋白的方法，分析蛋白分子构象的变化规律及其对酶解动力学特性的影响；通过甘薯肽片段释放规律研究、一级结构表征及抗氧化活性变化分析，探讨高静压下酶解甘薯抗氧化肽的构效关系；通过体内及体外评价探索甘薯肽发挥抗血管紧张素II诱导的氧化应激作用信号传导途径（NF-κB和PI3K/AKT），从而揭示其分子机制，为甘薯肽在功能食品中的应用提供理论基础，为具有抗氧化应激作用活性肽的研发提供新思路和方案。

高血压严重危害人类健康，血管紧张素II诱导的氧化应激在其发病机制中发挥重要作用，而生物活性肽通过抗氧化应激可能提供防治高血压新途径。甘薯蛋白是植物源活性肽的潜在来源，甘薯酶解肽具有一定的抗氧化活性及降血压作用，而高静压下酶解能显著提高其活性，但作用机制尚不明确。为深入研究上述作用机制，本项目采用高静压下酶解甘薯蛋白的方法，研究了甘薯蛋白的三维结构、二级结构、表面疏水性、水解特性及其酶解产物抗氧化活性等随高静压处理压力及加压时间的变化规律。高静压处理（100-300 MPa）显著提高了甘薯蛋白酶解产物的水解度和抗氧化活性，其中300 MPa下酶解60 min时甘薯蛋白酶解产物的水解度最高，所得酶解产物具有良好的抗氧化活性。通过甘薯肽片段释放规律研究、一级结构表征及抗氧化活性变化分析，探讨高静压下酶解甘薯抗氧化肽的构效关系，得到5个具有较高抗氧化活性的多肽片段，依次为：HDSASGQY ≥ YYMVSA ≥ HDSESGQY ~ YYIVS ~ RYYDPL，其活性可归因于组氨酸和酪氨酸的存在。通过体内及体外评价探索甘薯肽发挥抗血管紧张素II诱导的氧化应激作用，发现高、中、低剂量甘薯肽均显示了一定的抗血管紧张素II诱导的血压升高的作用，且不同浓度甘薯肽可显著提高血管紧张素II诱导损伤的人脐静脉内皮细胞存活率，可能的原因是甘薯肽可降低血管紧张素II诱导的大鼠体内及人脐静脉内皮细胞内的活性氧水平。本项目研究为甘薯肽在功能食品中的应用提供理论基础，为具有抗氧化应激作用活性肽的研发提供新思路和方案。