基于MAPK胰岛素信号通路探讨蒲黄总黄酮对血管平滑肌细胞增殖影响的机制

项目名称： 基于MAPK胰岛素信号通路探讨蒲黄总黄酮对血管平滑肌细胞增殖影响的机制

项目编号： No.81460711

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： 冯晓桃

作者单位： 广西中医药大学

项目金额： 47万元

中文摘要： 动脉粥样硬化是2型糖尿病大血管病变的病理生理学基础，而高胰岛素血症诱发血管平滑肌细胞增殖是其发生发展的重要机制，并由MAPK胰岛素信号通路所调控。活血化瘀是治疗 2 型糖尿病大血管病变的关键治则，研究表明广泛用于治疗2型糖尿病的活血化瘀中药蒲黄提取物蒲黄总黄酮（PTF）能抑制血管平滑肌细胞增殖，具有抗动脉粥样硬化的作用，但机制尚未清楚。本项目采用高浓度胰岛素模拟 2 型糖尿病高胰岛素血症诱导建立血管平滑肌细胞增殖细胞模型，观察PTF对该模型细胞增殖的影响，并采用 Western blot、基因芯片、Real-time PCR 等技术分析PTF对该模型细胞相关信号分子ERK1/2、p38MAPK、JNK等蛋白及基因表达的影响，进而从 MAPK 胰岛素信号通路阐明PTF抑制血管平滑肌细胞增殖的分子机制，为临床应用蒲黄和开发PTF新剂型防治 2 型糖尿病动脉粥样硬化性疾病提供科学依据。

中文关键词： 中医药；蒲黄总黄酮；动脉粥样硬化；血管平滑肌细胞；MAPK胰岛素信号通路

英文摘要： Atherosclerosis is pathophysiological basis of type 2 diabetic macroangiopathy, and vascular smooth muscle cell proliferation induced by hyperinsulinemia, which is regulated by mitogen-activated protein kinase (MAPK) insulin signal pathway, is the key mechanism during the development of atherosclerosis. Promoting blood circulation and removing blood stasis are the key therapy for macroangiopathy of type 2 diabetes, studies indicated that Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, a Chinese medicine which functions to promote blood circulation and to remove blood stasis and is widely used to treat type 2 diabetes, inhibits vascular smooth muscle cell proliferation, suggesting the action of anti-atherosclerosis, but the mechanisms remain unclear. This study aims to investigate the effect of PTF on the proliferation of vascular smooth muscle cells induced by high insulin level in vitro, which is similar to hyperinsulinemia of type 2 diabetes in vivo, and to analyze the effects of PTF on the protein and gene expression of signal molecules including ERK1/2, p38MAPK, JNK in the cells using Western blot, Gene chip, Real-time PCR and so on, thus revealing the molecular mechanisms of the inhibition of vascular smooth muscle cell proliferation by PTF through MAPK insulin signaling, which will provide scientific evidence for the clinical application of pollen Typhae and the development of new forms of PTF in preventing and treating the diseases of type 2 diabetic atherosclerosis.

英文关键词： traditional Chinese medicine;Pollen Typhae total flavone;atherosclerosis;vascular smooth muscle cells;MAPK insulin signaling