大豆皂苷I及类似物抑制成熟自由肾素以及干预（前）肾素-受体系统的机理研究

项目名称： 大豆皂苷I及类似物抑制成熟自由肾素以及干预（前）肾素-受体系统的机理研究

项目编号： No.31201289

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 膳食与营养

项目作者： 光翠娥

作者单位： 江南大学

项目金额： 27万元

中文摘要： 肾素是RAS的限速酶，它通过肾素-ACE-AngII-AT1R轴诱导高血压和CVD。表面等离子共振确定结合、解离常数和亲和力，NMR确定作用前后质子弛豫速率、质子间交叉弛豫速率、分子运动相关时间和转移NOE 等的变化，分子对接确定作用位点、作用力类型和结合自由能，CoMFA和CoMSIA分析建立3D-QSAR模型，确定立体、静电、疏水和氢键场三维等势图,揭示大豆皂苷I及类似物抑制成熟自由肾素的分子机理。 受体非酶激活的前肾素和与受体结合的肾素不仅促进AngI产生（酶），还上调促纤维因子表达（激素）。研究确定大豆皂苷I(或II)与和受体结合的（前）肾素作用的动力学和亲和力、抑制（前）肾素-受体降解Ang原的形式和Ki、皂苷-肾素与受体的亲和力，RT-qPCR确定主动脉HSMC受体、TGF-β、PAI-1和1型胶原mRNA表达量变化，揭示大豆皂苷对（前）肾素-受体系统两种信号功能的干预机制。

中文关键词： 大豆皂苷；肾素；受体；高血压；促纤维化因子

英文摘要： Renin is the rate-limiting step of the renin-angiotensin system (RAS) and can induce hypertension and cardiovascular diseases through the over-activated renin-ACE-AngII-AT1R axis.Real-time binding of the inhibitor soyasaponin I (or II)to renin is observed using surface plasmon resonance ,and the association (ka) and dissociation(kd) rate constants are measured and the dissociation constant (KD) is determined through the Langmuir 1:1 kinetic-binding model.Nuclear magnetic resonance is used to acquire the nonselective,selective and double selective spin-lattice relaxation rates of protons, and the molecular motional correlation times and 2D transferred nuclear overhauser enhancement of proton pairs in soyasaponin I (or II) in the absence and presence of renin,which will indicate affinity and active sites of interaction. Molecule docking analysis explores active sites, types (such as hydrogen bond,van der Waals,hydrophobic and ionic interactions), and energy of the interaction. Comparative molecular field analysis and comparative molecular similarity index analysis establish 3D-QSAR models through which the active sites and activities of renin inhibitory saponins can be easily obtained.These results will systematically show how soyasaponin I and its analogues exert their inhibitoy effects on mature/free renin. Bin

英文关键词： soyasaponin；renin；renin receptor；hypertension；profibrotic genes