Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning, China.
China Medical University, Shenyang, China.
J Int Med Res. 2020 Jun;48(6):300060520926065. doi: 10.1177/0300060520926065.
Migration of macrophages and atherosclerosis result in various diseases, including coronary heart disease. This study aimed to clarify the roles that ghrelin and Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) play in migration of macrophages under chronic intermittent hypoxia (CIH).
A rat model of CIH was constructed and changes in ghrelin and ROCK2 protein expression were measured by western blot assay. The migratory ability of macrophages was determined by the transwell assay. Hematoxylin and eosin staining was applied to detect the changes in intima-media thickness.
We found that CIH enhanced migration of macrophages, and this effect was attenuated by exogenous ghrelin. Additionally, the facilitative effect of CIH on migration of macrophages was strengthened or decreased by upregulation or downregulation of ROCK2, respectively. This phenomenon indicated that ROCK2 was involved in CIH-induced migration in macrophages. Furthermore, western blot and transwell assays showed that ghrelin inhibited CIH-induced migration via ROCK2 suppression in macrophages.
In summary, the present study shows that ghrelin inhibits CIH-induced migration via ROCK2 suppression in macrophages. Our research may help lead to identifying a new molecular mechanism for targeted therapy of atherosclerosis and its associated coronary artery diseases under intermittent hypoxia.
巨噬细胞的迁移与动脉粥样硬化导致了多种疾病，包括冠心病。本研究旨在阐明胃饥饿素和 ROCK2 在慢性间歇性低氧（CIH）诱导的巨噬细胞迁移中的作用。
通过western blot 检测构建的 CIH 大鼠模型中胃饥饿素和 ROCK2 蛋白表达的变化。通过 Transwell 测定巨噬细胞的迁移能力。苏木精和伊红染色检测内膜-中膜厚度的变化。
我们发现 CIH 增强了巨噬细胞的迁移，而外源性胃饥饿素可减弱这种作用。此外，通过上调或下调 ROCK2，分别增强或减弱 CIH 对巨噬细胞迁移的促进作用，表明 ROCK2 参与了 CIH 诱导的巨噬细胞迁移。此外，western blot 和 Transwell 实验表明，胃饥饿素通过抑制 ROCK2 抑制 CIH 诱导的巨噬细胞迁移。
综上所述，本研究表明胃饥饿素通过抑制 ROCK2 抑制 CIH 诱导的巨噬细胞迁移。我们的研究可能有助于确定靶向治疗间歇性低氧相关动脉粥样硬化及其相关冠状动脉疾病的新分子机制。
