PICU, First hospital of Jilin University, Changchun, 130021, Jilin, China.
Department of Respiration, First hospital of Jilin University, Changchun, 130021, Jilin, China.
Biomed Pharmacother. 2019 Jan;109:468-474. doi: 10.1016/j.biopha.2018.10.016. Epub 2018 Nov 3.
Cardiovascular complications are the main causes of mortality in diabetic patients. Teneligliptin is a newly developed anti-diabetic agent. It has been reported that teneligliptin has a vascular protective capacity in preclinical studies and diabetes patients. In this study, we investigated the effect of teneligliptin on hypoxia/reoxygenation (H/R)-induced endothelial cell injury in rat cardiac microvascular endothelial cells (CMECs). We showed that teneligliptin pretreatment suppressed H/R-induced production of reactive oxygen species (ROS), NADPH oxidase 4 (NOX4) expression and promoted glutathione production. Teneligliptin pretreatment reduced H/R-induced LDH release and improved cell viability. Teneligliptin significantly relieved the reduction in mitochondrial membrane potential (MMP) induced by H/R. Moreover, teneligliptin suppressed H/R-induced cytokine production and production of vascular adhesion molecules such as IL-1β, TNF-α and ICAM-1. Mechanistically, we showed that teneligliptin inhibited the expression of transcriptional factor Egr-1, which regulates cytokine production and vascular adhesion. Collectively, our data support the notion that teneligliptin is a protective agent in CMECs and has the potential for therapeutic use in the treatments of vascular complications in diabetes patients.
心血管并发症是糖尿病患者死亡的主要原因。替格列汀是一种新开发的抗糖尿病药物。有研究报道称，替格列汀在临床前研究和糖尿病患者中具有血管保护作用。在本研究中，我们研究了替格列汀对大鼠心脏微血管内皮细胞（CMEC）缺氧/复氧（H/R）诱导的内皮细胞损伤的作用。结果表明，替格列汀预处理可抑制 H/R 诱导的活性氧（ROS）、NADPH 氧化酶 4（NOX4）表达的产生和促进谷胱甘肽的产生。替格列汀预处理可减少 H/R 诱导的乳酸脱氢酶（LDH）释放，提高细胞活力。替格列汀可显著缓解 H/R 引起的线粒体膜电位（MMP）降低。此外，替格列汀可抑制 H/R 诱导的细胞因子产生和血管黏附分子如白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和细胞间黏附分子-1（ICAM-1）的产生。机制上，我们发现替格列汀可抑制转录因子 Egr-1 的表达，从而调节细胞因子产生和血管黏附。综上，我们的数据支持替格列汀是 CMECs 的保护剂，并有可能用于治疗糖尿病患者的血管并发症。
