阻塞性睡眠呼吸暂停(OSA)是睡眠期间的呼吸障碍,具有最突出的慢性间歇性缺氧(CIH)特征,诱导活性氧(ROS)的产生,从而破坏多种组织并引起代谢紊乱。在这项研究中,我们建立了不同程度的CIH(12.5%O2,10%O2,7.5%O2和5%O2)的OSA大鼠模型12周,发现CIH刺激胰岛素分泌,降低胰岛素:胰腺组织中的胰岛素原比例,并以剂量依赖的方式引起胰腺组织病变和细胞凋亡。此外,CIH促进肿瘤坏死因子(TNF)-α的产生,白细胞介素(IL)-1β和IL-6和活化的丝裂原活化蛋白激酶(MAPK)家族成员,细胞外调节蛋白激酶(ERK),c-Jun氨基末端激酶(JNK),和P38,取决于O2浓度。总之,CIH胰岛素分泌紊乱,引起炎症,病变,和胰腺组织细胞凋亡通过MAPK信号通路,对OSA和2型糖尿病(T2DM)的临床治疗具有重要意义。
Obstructive sleep apnea (OSA) is a breathing disorder during sleep, with a most prominent character of chronic intermittent hypoxia (CIH), which induces the generation of reactive oxygen species (ROS) that damages multiple tissues and causes metabolic disorders. In this study, we established a rat model of varying OSA with different grades of CIH (12.5% O2, 10% O2, 7.5% O2, and 5% O2) for 12 weeks, and found that CIH stimulated insulin secretion, reduced the insulin:proinsulin ratio in pancreatic tissue, and caused pancreatic tissue lesions and cell apoptosis in a dose-dependent manner. Moreover, CIH promoted the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and activated mitogen-activated protein kinase (MAPK) family members, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and P38, depending on the O2 concentration. In summary, CIH disturbed insulin secretion, and caused inflammation, lesions, and cell apoptosis in pancreatic tissue via the MAPK signaling pathway, which may be of great significance for clinical treatment of OSA and type 2 diabetes mellitus (T2DM).