新疆维药芹菜根抗高脂血症的药效物质基础及其作用机制研究

项目名称： 新疆维药芹菜根抗高脂血症的药效物质基础及其作用机制研究

项目编号： No.81460590

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 田莉

作者单位： 新疆医科大学

项目金额： 47万元

中文摘要： 新疆维医临床习用伞形科植物旱芹(Apium graveolens L.)的干燥根治疗头痛头晕，四肢麻木，高血压等症。前期研究发现维药芹菜根的乙酸乙酯和正丁醇萃取部位具有明显的调脂护肝、降压作用，并分离获得了黄酮、甾醇、苷类等10个成分，但其抗高脂血症的有效成分和作用机理尚不清楚。 . 本研究以柱层析、制备液相、MS、NMR等分离鉴定技术结合含大鼠载脂蛋白apo-AⅠ及其受体SR-BⅠ基因的酵母双杂交系统，定向筛选、追踪芹菜根抗高脂血症有效部位中的活性成分；采用Caco-2细胞模型研究活性成分的膜吸收特性，为有效成分的确定提供药动学依据；采用RT-PCR技术研究有效成分含药血清对肝细胞胆固醇代谢的吸收、合成、转化各环节相应靶点LDL-R、HMG-CoA 还原酶和CYP7A1 mRNA表达的影响，从分子水平研究其多部位、多靶点的综合调脂机理，为从维药芹菜根中开发防治高脂血症的口服药物提供研究基础。

中文关键词： 芹菜根；高脂血症；有效成分；胆固醇代谢；作用机理

英文摘要： Apium graveolens L. belongs to umbelliferous plant. The dry root of Apium graveolens L. is commonly used as a traditional Uygur medicine in xinjiang for treatment of headache，dizziness，numbness of limbs，high blood pressure. Previous research has shown that the ethyl acetate extraction and n-butanol extraction of Apium graveolens L. root have obvious regulating blood lipids，protect liver and antihypertensive activity. Meanwhile，ten chemical constituents，including flavonoids，sterol and glycosides，were isolated. At present，the effective constituents of anti-hyperlipidmia of Apium graveolens L. root and its action mechanism are still unclear. Based on previous research results，some separation and detection technology，including column chromatography，preparative HPLC，MS、NMR and so on，combined yeast two-hybrid system，which carry apolipoprotein AI (apo-AI) and scavenger receptors class B type I (SR-BI) genes of rat，will be applied to directed screening the active constituents of anti-hyperlipidemia from anti-hyperlipidmia effective part of Apium graveolens L. root. The film absorption characteristics of active components were researched by Caco-2 cell model, which will provide the pharmacokinetic basis of effective constituents. The mechanism of regulating blood lipids will be systematically investigated based on the multi-site, multi-targe on the molecular level. RT-PCR technology was adopted to study the influence of serum containing the active constituents on the main parts of the cholesterol metabolism such as the absorption, synthesis and transofrmation in liver cells by means of observing the expressions of LDL-R, HMG-CoA reductase and CYP7A1 mRNAs at different time points. It will provide experimental basis for the research and development of anti-hyperlipidmia oral drug from Apium graveolens L. root in the future.

英文关键词： Apium graveolens L;anti-hyperlipidmia;the effective constituent;cholesterol metabolism;mechanism