Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People's Republic of China.
Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Shijiazhuang, Hebei, People's Republic of China.
PLoS One. 2024 Mar 7;19(3):e0296792. doi: 10.1371/journal.pone.0296792. eCollection 2024.
Chronic intermittent hypoxia (CIH) may play an important role in the development of diabetic cardiomyopathy (DCM). However, the exact mechanism of CIH-induced myocardial injury in DCM remains unclear. In vivo, the db/db mice exposed to CIH were established, and in vitro, the H9C2 cells were exposed to high glucose (HG) combined with intermittent hypoxia (IH). The body weight (BW), fasting blood glucose (FBG) and food intake were measured every two weeks. The glycolipid metabolism was assessed with the oral glucose tolerance test (OGTT) and insulin resistance (IR). Cardiac function was detected by echocardiography. Cardiac pathology was detected by HE staining, Masson staining, and transmission electron microscopy. The level of reactive oxygen species (ROS) in myocardial tissue was detected by dihydroethidium (DHE). The apoptosis was detected by TUNEL staining. The cell viability, ROS, and the mitochondrial membrane potential were detected by the cell counting kit-8 (CCK-8) assay and related kits. Western blotting was used to analyze the liver kinase B1/AMP-activated protein kinase/ nuclear factor-erythroid 2-related factor 2 (LKB1/AMPK/Nrf2) signaling pathway. CIH exposure accelerated glycolipid metabolism disorders and cardiac injury, and increased the level of cardiac oxidative stress and the number of positive apoptotic cells in db/db mice. IH and HG decreased the cell viability and the level of mitochondrial membrane potential, and increased ROS expression in H9C2 cells. These findings indicate that CIH exposure promotes glycolipid metabolism disorders and myocardial apoptosis, aggravating myocardial injury via the LKB1/AMPK/Nrf2 pathway in vitro and in vivo.
慢性间歇性低氧（CIH）可能在糖尿病心肌病（DCM）的发展中起重要作用。然而，CIH 诱导 DCM 心肌损伤的确切机制尚不清楚。在体内，建立了 CIH 暴露的 db/db 小鼠模型，在体外，将 H9C2 细胞暴露于高葡萄糖（HG）联合间歇性低氧（IH）中。每两周测量一次体重（BW）、空腹血糖（FBG）和食物摄入量。通过口服葡萄糖耐量试验（OGTT）和胰岛素抵抗（IR）评估糖脂代谢。通过超声心动图检测心功能。通过 HE 染色、Masson 染色和透射电镜检测心脏病理学。通过二氢乙啶（DHE）检测心肌组织中活性氧（ROS）的水平。通过 TUNEL 染色检测细胞凋亡。通过细胞计数试剂盒-8（CCK-8）测定和相关试剂盒检测细胞活力、ROS 和线粒体膜电位。Western blot 用于分析肝激酶 B1/AMP 激活蛋白激酶/核因子-红细胞 2 相关因子 2（LKB1/AMPK/Nrf2）信号通路。CIH 暴露加速了糖脂代谢紊乱和心脏损伤，并增加了 db/db 小鼠心脏氧化应激水平和阳性凋亡细胞数量。IH 和 HG 降低了细胞活力和线粒体膜电位水平，并增加了 H9C2 细胞中 ROS 的表达。这些发现表明，CIH 暴露通过体外和体内的 LKB1/AMPK/Nrf2 通路促进糖脂代谢紊乱和心肌细胞凋亡，加重心肌损伤。
