赤芍川芎有效部位对波动高血糖介导血管内皮损伤过程中血小板活化及PKCβ1表达的影响

高血糖是动脉粥样硬化的独立危险因素，血管内皮功能异常是其心血管病变的病理生理基础。波动高糖较稳定高糖更易引起血管内皮的损伤。糖尿病患者以高粘血症为特征的血液流变学改变是中医"血瘀"的具体体现之一。课题组前期发现PKCβ1作为冠心病血瘀证的目标分子之一，在波动高糖引起血管内皮损伤过程中扮演关键角色，同时发现PKCβ1高表达也参与了血小板活化过程。研究证实活血化瘀制剂芎芍胶囊具有抗血小板聚集、保护血管内皮功能的作用，在抗动脉粥样硬化方面疗效确定。本研究借助波动高糖培养人脐静脉内皮细胞与人血小板建立实验体系，体内以波动高糖大鼠模型为研究对象，以PKCβ1为切入点，观察在血管内皮损伤过程中血小板活化和PKCβ1的表达变化及赤芍川芎有效部位的干预效应，探讨PKCβ1在波动高糖继发血管病变中的作用及活血化瘀制剂的作用靶点，为活血化瘀药物防治糖尿病的临床应用提供实验依据。

Hyperglycemia is an independent risk factor for atherosclerosis. Vascular endothelial injury is termed as one of the most important pathophysiologic basis of hyperglycemia. Compared to consistent high glucose, fluctuant high glucose is more likely to cause vascular endothelial injury. High blood hyperviscosity, a main hemodynamics change in diabetes patients, is regarded as a specific feature of 'blood stasis' according to the theory of Traditional Chinese Medicine. Our previous studies have shown that protein kinase C beta 1 (PKCβ1) as a target molecule of coronary heart disease with blood stasis syndrome plays a key role in pathogenesis of vascular endothelial injury induced by fluctuant high glucose. Meanwhile, high level of PKCβ1 expression is involved in platelet activation. Previous studies have shown that effective components of Chuanxiong Rhizome and Peony Root represent a robust inhibitory influence on platelet aggression and endothelial injury. In the current study, we therefore investigate PKCβ1-induced molecular events that might be responsible for the platelet activation in vascular endothelial injury induced by fluctuant high glucose using human platelet and umbilical vein endothelial cells in vitro and type 2 diabetes mellitus rats model in vivo. Meanwhile, the effects of effective components of Chuanxiong Rhizome and Peony Root on vascular endothelial injury and platelet activation are also investigated. We aim to explore the exact role of PKCβ1 in the vascular secondary changes induced by fluctuant high glucose and the mechanisms of promoting blood circulation and removing blood stasis drugs, meanwhile provide experimental evidences for their clinical uses in diabetes mellitus prevention and treatment.