自噬与内质网应激的交互效应在慢性间歇性低氧介导的2型糖尿病动脉粥样硬化形成中的作用及活血化瘀中药的调控机制

慢性间歇性低氧（CIH）可加重2型糖尿病（T2DM）血管内皮损伤，促进动脉粥样硬化（AS）进展，但其机制尚不明确，成为研究热点。课题组前期研究发现合并阻塞性睡眠呼吸暂停综合征（OSAS）的T2DM患者体内存在自噬与内质网应激的交互效应，推测其可能在CIH介导的T2DM-AS形成中扮演了重要角色。合并OSAS的T2DM患者存在血液高凝状态与中医“血瘀”密切相关。前期研究证实活血化瘀中药川芎的有效成分川芎嗪血管内皮保护及抗AS疗效确切。本研究体外借助CIH复合高糖高脂诱导建立人脐静脉内皮胰岛素抵抗（IR）细胞模型，在体借助CIH复合链脲佐菌素腹腔注射及高脂饲料喂养诱导ApoE基因敲除小鼠建立T2DM-IR-AS动物模型，探明CIH介导T2DM-AS形成的分子机制及与IRE1α/XBP1信号通路的相关性及川芎嗪的干预效应，为活血化瘀中药防治OSAS合并糖尿病血管病变的临床应用提供实验证据。

Chronic intermittent hypoxia (CIH) can aggravate vascular endothelium damage and promote the development of atherosclerosis(AS) of Type 2 Diabetes(T2DM), but the related mechanisms are unclear, which become a hot research topic.Our previous studies have shown that crosstalk between endoplasmic reticulum stress and autophagy in the patients of T2DM with obstructive sleep apnea syndrome (OSAS), infer that the crosstalk plays an important role in the development of CIH-induced T2DM-AS. Hypercoagulable state of T2DM patients with OSAS is regarded as a specific characteristic of "Blood stasis" on the basis of traditional Chinese medicine. Previous studies have shown that Tetramethylpyrazine (TMP), an bioactive component of Chuanxiong, has certain effect on protect vascular endothelial and anti-AS. In the current study, we investigate the molecular mechanism and the role of IRE1α/XBP1 in insulin resistance models of vascular endothelial cell in vitro induced by CIH & high glucose and hyperlipidemia, while in T2DM-IR-AS model of ApoE-/- rats induced by CIH & streptozotocin and fat dietary feed in vivo. Meanwhile, the regulating effects of TMP is also investigated. To provide experimental evidence for its clinical application in the prevention and treatment of OSAS-related T2DM-AS.