蜂胶影响细菌内毒素诱导的血管内皮细胞自噬的分子机制研究

项目名称： 蜂胶影响细菌内毒素诱导的血管内皮细胞自噬的分子机制研究

项目编号： No.31201860

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 畜牧学与草地科学、兽医学、水产学

项目作者： 玄红专

作者单位： 聊城大学

项目金额： 23万元

中文摘要： 蜂胶具有较好的抗炎功效，但作用机制尚未彻底阐明。血管内皮细胞（VEC）功能损伤或紊乱会导致包括炎症在内的多种疾病的发生。本课题组前期研究中发现低浓度的蜂胶降低Toll样受体4（TLR4）的表达和磷脂酰胆碱特异性磷脂酶C（PC-PLC）的活性，抑制细菌内毒素（LPS）诱导的VEC损伤，但在此过程中，蜂胶并不是通过抑制VEC凋亡的方式起到保护作用，随后我们发现蜂胶降低LPS诱导的VEC中自噬标志LC3-Ⅱ的水平。我们推测蜂胶可能是通过抑制细胞自噬的方式保护LPS对VEC的损伤，这可能是蜂胶抗炎的一种新的作用机制。为了证实这一假说，本课题拟通过体外LPS诱导VEC自噬性损伤复制炎症模型，以参与VEC自噬的关键因子-膜整连蛋白β4、ANXA7、BIRC2、TLR4、ROS为切入点，从细胞和分子水平揭示蜂胶对VEC自噬的影响，阐明蜂胶的抗炎作用机制，并为蜂胶抗炎作用研究提供新思路和新靶点。

中文关键词： 蜂胶；自噬；脂多糖；血管内皮细胞；抗炎

英文摘要： Propolis has been reported to possess good anti-inflammatory effect, however, the mechanisms are not fully elaborated. Vascular endothelial cell (VEC) damage or dysfunction is important in many diseases, including inflammation. We previously found that low concentration of propolis could protect VEC induced by lipopolysaccharide (LPS) through decreasing the expression of Toll like receptor 4 (TLR4) and the activity of phosphatidylcholine-specific phospholipase C (PC-PLC), but the protect effect wasn't through inhibiting VEC apoptosis, then we also found that propolis could decrease the level of LC3-Ⅱ, an autophagy marker. We speculated propolis protecting VEC induced by LPS was through autophagy, which could be a new mechanism of propolis on anti-inflammatory effect. To test this hypothesis, we are planning to induce VEC autophagy induced by LPS to copy inflammatory model, and the key factors of VEC autophagy - integrin β4, ANXA7, BIRC2, TLR4 and reactive oxygen species (ROS) are as the breakthrough point to disclose the effect of propolis on autophagy of VEC and clarify the mechanism of propolis on anti-inflammatory effect, which would supply new ideas and new targets for propolis on anti-inflammatory effect.

英文关键词： propolis；autophagy；lipopolysaccharide；vascular endothelial cell；anti-inflammation