Tetramethylpyrazine attenuates chronic intermittent hypoxia-exacerbated diabetic atherosclerosis: a mechanistic study of the IRE1α-XBP1 signaling pathway

作者：Binyu Luo, Wenting Wang, Yiwen Li, Jing Cui, Qian Xu, Mengmeng Zhu, Yanfei Liu, Yue Liu · 发表于：Acupuncture and Herbal Medicine · 年份：2025 · DOI：10.1097/hm9.0000000000000154 · 被引用次数：11 · 研究领域：Peroxisome Proliferator-Activated Receptors、Eicosanoids and Hypertension Pharmacology、Cardiovascular, Neuropeptides, and Oxidative Stress Research

Objective: A complex relationship exists between obstructive sleep apnea syndrome and diabetes mellitus (DM). Chronic intermittent hypoxia (CIH), which is a core pathological feature of obstructive sleep apnea syndrome, may play an important role in the onset and development of DM-related atherosclerosis (DM-AS). This study aimed to investigate the mechanism of action of tetramethylpyrazine (TMP) in CIH-associated DM-AS. Methods: In vivo , a DM-AS mouse model was established by intraperitoneal injection of streptozotocin combined with a high-fat diet. They were exposed to CIH or normoxic conditions for 8 weeks and received different doses of TMP, rosuvastatin, toyocamycin, and purified water. Glycolipid metabolism, inflammation levels, degree of aortic AS, and expression levels of endoplasmic reticulum stress (ERS) and autophagy proteins were examined in mice. In vitro , human umbilical vein endothelial cells (HUVECs) were treated with high glucose and fat in combination with insulin to establish an insulin-resistant cell model (HUVEC-IR). After pretreatment with 4μ8C (IRE1 inhibitor) and different doses of TMP, intermittent hypoxic intervention was performed. Changes in cell morphology, proliferative activity, glucose consumption, and ability to migrate were observed, and the expression levels of ERS and autophagy proteins were detected. Results: In vivo experiments showed that CIH significantly increased blood glucose levels and Homeostasis Model Assessment of Insulin Resis...