Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
PLoS One. 2012;7(4):e35007. doi: 10.1371/journal.pone.0035007. Epub 2012 Apr 6.
Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms.
Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-α and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs.
Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes.
最近有研究表明，增强肠促胰岛素效应可改善心脏功能。我们研究了二肽基肽酶-4（DPP-4）抑制剂地氟噻嗪对球囊损伤后颈动脉再狭窄的发生及相关机制的影响。
将 Otsuka Long-Evans Tokushima Fatty 大鼠分为四组：对照组（生理盐水）和地氟噻嗪 100、250 和 500mg/kg/天组（每组 10 只）。地氟噻嗪或生理盐水于颈动脉损伤前 1 周开始口服，持续至损伤后 2 周。治疗 3 周后，地氟噻嗪治疗可显著降低肥胖型糖尿病大鼠的内-中膜厚度比（IMR），呈剂量依赖性。该作用伴随着葡萄糖稳态的改善、循环中高敏 C 反应蛋白（hsCRP）水平的降低和脂联素水平的升高。此外，IMR 的降低与 hsCRP、肿瘤坏死因子-α和单核细胞趋化蛋白-1 水平以及纤溶酶原激活物抑制剂-1 活性的降低显著相关。血管平滑肌细胞（VSMCs）的体外证据表明，地氟噻嗪治疗后细胞增殖和迁移明显减少。此外，地氟噻嗪还可增加 VSMCs 中的半胱天冬酶-3 活性，降低单核细胞黏附和 NFκB 激活。
地氟噻嗪对颈动脉损伤后的再狭窄具有保护作用，为治疗糖尿病大血管并发症提供了治疗意义。
