阻塞性睡眠呼吸暂停（OSA）导致的慢性间歇性低氧（CIH）可引起血管内皮损伤，促进动脉粥样硬化（AS）的发生发展，但CIH介导AS发生的机制尚不明确。血小板活化是AS形成的关键环节之一，OSA患者存在血小板活化状态与中医血瘀证密切相关。课题组前期研究发现PI3Kβ在OSA患者血小板上高表达，同时发现其参与血小板活化的过程。推测PI3Kβ可能在CIH介导AS的发生过程中扮演了重要角色。研究证实活血化瘀中药川芎的有效成分川芎嗪保护血管内皮、抗血小板及抗AS疗效肯定。本研究借助CIH诱导人血小板建立体外血小板活化模型，以CIH复合高脂饲料喂养ApoE基因敲除小鼠诱发AS动物模型，以PI3Kβ为切入点，观察CIH介导AS形成过程中血小板活化与PI3Kβ的表达变化及川芎嗪的干预效应，探讨PI3Kβ在其中的作用机制以及活血化瘀中药的作用靶点，为活血化瘀药物防治OSA继发血管病变的临床应用提供实验依据。

Obstructive sleep apnea (OSA) caused by chronic intermittent hypoxia (CIH) can cause vascular endothelium damage, promote the development of atherosclerosis (AS). How the CIH induced AS remains unclear. Platelet activation is one of the critical roles during the development of AS. High platelet activation situation among OSA patients is regarded as a specific characteristic of "Blood stasis"on the basis of traditional Chinese medicine. Our previous studies have shown that high PI3Kβ expression among OSA patients, while PI3Kβ is involved in the progress of platelet activation. We infer that PI3Kβ plays an important role in the development of CIH-induced AS. Previous studies have shown that Tetramethylpyrazine (TMP), an bioactive component of Chuanxiong, has certain effect on anti-platelet and anti-AS. In the current study, we investigate the role of PI3Kβ in human platelet activation model in vitro induced by CIH and in AS model of ApoE-/- rats induced by CIH and fat dietary feed in vivo. Meanwhile, the effects of TMP on platelet activation and vascular endothelial injury are also investigated. We aim to explore the role of PI3Kβ in the development of platelet activation during CIH-induced AS and the mechanism or target of activated blood circulation of Chinese drugs. To provide experimental evidence for their clinical application in the prevention and treatment of vascular secondary diseases induced by OSA.