Zhang Rui, Zou Zhiwei, Zhou Xiaojun, Shen Xue, Fan Zhengyuan, Xie Tianyue, Xu Chunmei, Liao Lin, Dong Jianjun
Division of Endocrinology, Department of Internal Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Division of Endocrinology, Department of Internal Medicine, Qilu Hospital of Shandong University, Shandong, China.
Cell Physiol Biochem. 2019;52(1):16-26. doi: 10.33594/000000002. Epub 2019 Feb 18.
BACKGROUND/AIMS: Diabetes affects the entire vascular system and accelerates atherosclerosis and ischemia. Percutaneous transluminal angioplasty with or without stenting is the main therapeutic strategies; however, the restenosis rate is high in diabetics. Sulfonylureas (SUs) are widely prescribed agents for the treatment of type 2 diabetes (T2DM) and function by interacting with sulfonylurea receptors (SURs), which also exists in vascular smooth muscle cells (VSMCs), give rise to the potential that SUs influence VSMCs. The proliferation and migration of VSMCs play important roles in the formations of primary stenosis and restenosis, especially the latter. However, there are no data about the exact effects of SUs on these processes.
Human aortic smooth muscle cells (HASMCs) were exposed to SUs prior to exposure to 30mM glucose. Cell proliferation was detected by CCK8 assay. Cell migration was detected by wound healing assay and transwell assay. Protein expression was determined by immunofluorescence and western blot. Diazoxide was used to evaluate the role of K channel in these processes.
The proliferation and migration of HASMCs were significantly aggravated by glibenclamide and glimepiride, and their effects were reversed by diazoxide. In contrast, above characteristics of HASMCs were apparently inhibited by gliclazide, and this was maintained after opening the K channel.
These results imply that K channels play an important part in proliferation and migration of VSMCs induced by glibenclamide and glimepiride. In contrast, the inhibitory effect of gliclazide on VSMCs appeared to have more potential for the prevention of vascular obstructive diseases in T2DM.
背景/目的：糖尿病会影响整个血管系统，加速动脉粥样硬化和局部缺血。经皮腔内血管成形术（无论是否置入支架）是主要治疗策略；然而，糖尿病患者的再狭窄率较高。磺脲类药物（SUs）是广泛用于治疗2型糖尿病（T2DM）的药物，通过与磺脲类受体（SURs）相互作用发挥作用，而磺脲类受体也存在于血管平滑肌细胞（VSMCs）中，这使得磺脲类药物有可能影响血管平滑肌细胞。血管平滑肌细胞的增殖和迁移在原发性狭窄和再狭窄的形成中起重要作用，尤其是后者。然而，关于磺脲类药物对这些过程的确切影响尚无数据。
在暴露于30mM葡萄糖之前，将人主动脉平滑肌细胞（HASMCs）暴露于磺脲类药物。通过CCK8测定法检测细胞增殖。通过伤口愈合测定法和Transwell测定法检测细胞迁移。通过免疫荧光和蛋白质印迹法测定蛋白质表达。使用二氮嗪评估钾通道在这些过程中的作用。
格列本脲和格列美脲显著加剧了HASMCs的增殖和迁移，而二氮嗪可逆转它们的作用。相比之下，格列齐特明显抑制了HASMCs的上述特性，并且在打开钾通道后这种抑制作用仍然存在。
这些结果表明钾通道在格列本脲和格列美脲诱导的血管平滑肌细胞增殖和迁移中起重要作用。相比之下，格列齐特对血管平滑肌细胞的抑制作用似乎在预防T2DM中的血管阻塞性疾病方面更具潜力。
