活血降糖饮通过Scrib/YAP对胰岛β细胞脂性凋亡的影响及机制

β细胞脂性凋亡是导致2型糖尿病发生发展的重要因素之一。近年来研究发现Hippo信号通路在调控细胞生长、凋亡方面具有重要作用，对β细胞亦有调控作用；而YAP的活化以及在细胞核内的变化决定了Hippo信号通路最终介导细胞生长还是细胞凋亡；有研究表明，Scrib蛋白具有调控YAP蛋白表达和活化的作用。项目组前期研究表明，脂毒性损伤大鼠体内Scrib蛋白下调，经活血降糖饮干预后恢复，基于此结果，我们大胆推测活血降糖饮能通过调节Scrib蛋白表达，影响YAP蛋白活性及在细胞核内的活动，从而抑制β细胞脂性凋亡。本研究以此为切入点，建立2型糖尿病大鼠模型，应用分子生物学、分子免疫学等技术，探讨脂毒性损伤对Hippo通路的影响，以及活血降糖饮的干预对Scrib/YAP蛋白表达、YAP的亚细胞定位等Hippo通路中关键的信号转导的影响，探讨活血降糖饮对脂毒性损伤的治疗作用以及对β细胞脂凋亡的保护作用和机制。

Islet β cell lipotoxic apoptosis plays vital role in development of type 2 diabetes. In recent research, Hippo pathway has been proved to control cell growth and apoptosis, including in β cell. In Hippo pathway, the activation and location in cell nuclear of YAP will determine cell growth or apoptosis, which is mediated by Scrib. In our previous research, Scrib was decreased in lipotoxic rats while up regulated by Huoxue-Jiangtang Decoction, so we presume that by regulating the expression of Scrib, Huoxue-Jiangtang Decoction will influence the activation and location of YAP, thus, inhibit β cell apoptosis. Based on the above, type 2 diabetes rat model will be applied in this study to investigate the impact of lipotoxicity on Hippo signal pathway, and the effect of Huoxue-Jiangtang Decoction on Scrib/YAP protein expression, YAP sub-cell location, so as to elucidate the therapeutic effect of Huoxue-Jiangtang Decoction on lipotoxicity and β cell apoptosis.