Department of Endocrine, Shanxian Central Hospital, Heze, Shandong, China.
Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):841-848. doi: 10.26355/eurrev_201901_16899.
The aim of this paper was to study sitagliptin in improving the endothelial-mesenchymal transition (EndMT) of human aortic endothelial cells (HAECs) and cardiac function of rats with diabetes mellitus (DM) and its possible pathway.
Sprague Dawley (SD) rats were divided into control group, DM group and sitagliptin group. The myocardial contraction and relaxation functions of rats in each group were observed via echocardiography. The changes in cardiac structure and fiber were observed via hematoxylin-eosin (HE) staining, Masson staining and Sirius red staining. The immunohistochemical assay was performed to observe the expressions of α-smooth muscle actin (α-SMA) and VE-cadherin in HAECs; the expression of reactive oxygen species (ROS) in HAECs was detected using the fluorescence probe. Moreover, the expressions of transforming growth factor-β1 (TGF-β1), phosphorylated-protein kinase A (p-PKA), PKA and extracellular signal-regulated kinase (ERK) were observed via Western blotting.
Sitagliptin could improve the myocardial contraction and relaxation functions in diabetic rats and EndMT and ROS production in HAECs. In the DM group, the expression of Glucagon-like peptide-1 (GLP-1) was decreased, while the expression of stromal-derived factor-1α (SDF-1α) was decreased and the expressions of downstream PKA/ERK pathway and TGF-β1 were increased. The above changes could be reversed by sitagliptin.
Sitagliptin can reverse the EndMT in HAECs as well as the cardiac function in diabetic rats through the SDF-1α/PKA pathway.
本文旨在研究西他列汀改善人主动脉内皮细胞（HAEC）内皮-间质转化（EndMT）和糖尿病大鼠心功能的作用及其可能机制。
SD 大鼠分为对照组、糖尿病组和西他列汀组。通过超声心动图观察各组大鼠心肌收缩和舒张功能的变化。通过苏木精-伊红（HE）染色、Masson 染色和天狼猩红染色观察心脏结构和纤维的变化。免疫组织化学法观察 HAEC 中α-平滑肌肌动蛋白（α-SMA）和血管内皮钙黏蛋白（VE-cadherin）的表达；荧光探针检测 HAEC 中活性氧（ROS）的表达。Western blot 法观察转化生长因子-β1（TGF-β1）、磷酸化蛋白激酶 A（p-PKA）、PKA 和细胞外信号调节激酶（ERK）的表达。
西他列汀可改善糖尿病大鼠的心肌收缩和舒张功能以及 HAEC 的 EndMT 和 ROS 产生。在糖尿病组中，胰高血糖素样肽-1（GLP-1）表达降低，基质衍生因子-1α（SDF-1α）表达降低，下游 PKA/ERK 通路和 TGF-β1 表达增加。西他列汀可逆转上述变化。
西他列汀可通过 SDF-1α/PKA 通路逆转 HAEC 的 EndMT 及糖尿病大鼠的心功能障碍。
