紫薯花青素调控内皮细胞老化的分子机制研究

项目名称： 紫薯花青素调控内皮细胞老化的分子机制研究

项目编号： No.31201039

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 孙春辉

作者单位： 江苏师范大学

项目金额： 23万元

中文摘要： 血管内皮细胞的老化可以诱发动脉硬化等衰老相关疾病，但老化的分子机制尚不明确。本课题组研究表明，caveolin-1和膜整联蛋白β4参与内皮细胞的老化，紫薯花青素(PSPC)可以延缓动脉硬化斑块的内皮老化，我们推断PSPC可能通过二者调控内皮细胞的衰老。为验证这一假设，我们拟进行以下研究：1)利用动脉硬化小鼠模型和人脐静脉血管内皮细胞培养体系，检测PSPC能否抑制内皮细胞老化；2)检测PSPC对老化内皮和斑块中caveolin-1和膜整联蛋白β4的影响，分析过表达或敲除该基因后对PSPC调控作用的影响，初步判断PSPC是否通过二者调控内皮细胞老化；3)分析caveolin-1与膜整联蛋白β4在内皮老化中的相互关系，并靶向下游信号，检测PSPC对其定位及活化的影响，最终提出PSPC调控内皮细胞老化的可能分子机制。为阐明内皮细胞老化分子机制提供实验依据，同时为内皮老化相关疾病的治疗提供新的靶点。

中文关键词： 类黄酮；内皮细胞；老化；NLRP3炎性小体；自噬

英文摘要： Senescence of vascular endothelial cells (VECs) plays important roles in the development of aging-related diseases such as atherosclerosis, however, the mechanisms underlying VECs senescence are still unclear. Our previous studies suggested that caveolin-1 and integrin β4 participated in the process of VECs senescence and purple sweet potato color (PSPC) could suppress aging of endoderm in the plaques of atherosclerosis. Based on these results, we deduced that PSPC could inhibit VECs senecence and regulate atherosclerosis through caveolin-1 and integrin β4. To prove this hypothesis, we plan to study as follows: 1)utilize the model of mice with atherosclerosis and culture system of human umbilical vein endothelial cells (HUVECs) to analyze whether PSPC inhibit VECs senescence and suppress the development of atherosclerosis in vivo and in vitro; 2)detect changes of caveolin-1 and integrin β4 in VECs and plaques of atherosclerosis after PSPC administration, and investigate effects of caveolin-1 and integrin β4 overexpression or knockdown on VECs senescence regulated by PSPC; 3)analyze the relationship between caveoin-1 and integrin β4 during VECs senescence, and test the effect of PSPC on the activation and distribution of signal molecules mediated by caveolin-1 and integrin β4, to further clarify the mechanisms o

英文关键词： flavonoid；endothelial cells；senescence；NLRP3 inflammasome；autophagy