玄参有效成分安格洛苷C的分离、提取及防治心室重构的作用研究

In TCM theory, Radix Scrophulariae has the effects of clearing away heat from the blood, nourish yin, purging fire, and relieving toxins. It has been proven in our previous research that Radix Scrophulariae has beneficial effect against ventricular remodeling through suppressing the excessive activation of sympathetic nervous system and renin-angiotensin-aldosterone system. On the basis of our previous research combining with the tracking analysis of efficacy experiment, based on the polarity distribution principle, we use the silica gel, macroporous absorption resin and solvent system to extract the effective component Angoroside C..Three kinds of animal models with ventricular remodeling are conducted for the experimental research: First is induced by subcutaneous injection of isoprenaline. Second is pressure overloaded ventricular remodeling model, which is induced by banding abdominal aorta. The third is achieved by coronary artery ligation..The RIA or ELISA is used to explore the effects of Angoroside C on neuroendocrine factors related to ventricular remodeling. The pathomorphological changes of myocardial tissues are observed and the expressions of cytokines are detected by immunohistochemical assay. And with the help of molecular biology, in the level of gene expression and signal transduction pathway, we analysis the role and the mechanism of Angoroside C in the prevention and treatment of ventricular remodeling caused by different reasons..In conclusion, the research will provide the way to batch extract and purify Angoroside C, the effective component in Radix Scrophulariae, which is beneficial to prevent and control ventricular remodeling. The research will also clarify the mechanism of Angoroside C. It may lay the foundation for the development and application of this effective component from Radix Scrophulariae.

在已探明凉血滋阴，泻火解毒中药玄参具有抑制交感神经和肾素－血管紧张素－醛固酮等神经内分泌系统过度激活、抗心室重构的基础上，结合药效实验追踪分析，应用极性分配原理，硅胶、不同型号大孔吸附树脂、溶剂系统分离、提取其有效成分。制备异丙肾上腺素致小鼠心肌纤维化、心室重构模型，压力超负荷及心肌梗死致大鼠心室重构模型。采用放射免疫或酶联免疫吸附法测定分离获得的安格洛苷C对心室重构相关的神经内分泌因子变化的影响；用病理组织形态学及免疫组化法分析对心肌组织结构的变化及相关细胞因子表达变化的影响；并采用分子生物学分析方法，在基因表达和信号转导通路水平分析有效成分防治不同原因所致心室重构的作用环节和机制。提供玄参中防治心室重构有效成分安格洛苷C批量提取、纯化的方法；阐明其作用环节和机制，为该有效成分的开发应用奠定基础。

在已探明凉血滋阴，泻火解毒中药玄参具有抑制交感神经和肾素－血管紧张素－醛固酮等神经内分泌系统过度激活、抗心室重构的基础上，结合药效实验追踪分析，应用极性分配原理，硅胶、不同型号大孔吸附树脂、溶剂系统分离、提取其有效成分。制备异丙肾上腺素致小鼠心室重构模型，压力超负荷及心肌梗死致大鼠心室重构模型。采用放射免疫或酶联免疫吸附法测定分离获得的安格洛苷C对心室重构相关的神经内分泌因子变化的影响；用病理组织形态学及免疫组化法分析对心肌组织结构的变化及相关细胞因子表达变化的影响；并采用分子生物学分析方法，在基因表达和信号转导通路水平分析有效成分防治不同原因所致心室重构的作用环节和机制。.经过实验研究，我们成功从玄参中提取出得率约为生药千分之一的提取物，并经结构分析其主要成分为安格洛苷C，其抗异丙肾上腺素致小鼠心室重构的活性接近玄参生药的1000倍。经过改进有效成分最佳洗脱条件，提高纯度，目前已成功提取分离纯化两批，共获得安格洛苷C(>95%)31.25克。.后经不同模型药效学实验证明，安格洛苷C具有较明显的抗心室重构的活性作用，它可以显著降低大鼠的心脏质量指数，抑制血清醛固酮水平和心肌AngⅡ和ET-1的含量，并显著缩小心肌细胞横断面面积，抑制Ⅰ、Ⅲ型胶原纤维沉积，降低MMP-2、MMP-9含量并提高TIMP-1水平。安格洛苷C还能显著降低心肌TGF-β1，AT1R，α-SMA，ET-1等基因的过表达。且较小的剂量即能发挥较大的作用，其抗心室重构的作用机制可能是通过抑制成纤维细胞增殖，并通过调节炎症因子表达而完成的。.本课题提供玄参中安格洛苷C批量提取、纯化的方法；并经实验证明安格洛苷C的确对防治心室重构产生作用，分析其可能产生的作用环节和机制，为该有效成分的开发应用奠定基础，也为传统中药的重新开发利用提供新思路，为人类防治心衰提供新方法。

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