Biotherapy Center, Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Department of Pharmacology (State‑Province Key Laboratories of Biomedicine‑Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8003-8010. doi: 10.3892/mmr.2017.7667. Epub 2017 Sep 29.
The present study evaluated the effect of anagliptin on intimal hyperplasia following carotid artery injury in Sprague‑Dawley rats. Sprague‑Dawley rats weighing 280‑300 g were injured using a 2F Fogarty balloon embolectomy catheter. The rats were divided into injury‑(saline) and anagliptin‑(10 mg/kg/day) treated groups. vascular injuries were induced in the left carotid artery, followed by evaluation of neointima formation at 28 days. The right and left carotid arteries were harvested and evaluated with histological evaluation, and the plasma activity of glucagon‑like peptide 1 receptor (GLP‑1), stromal cell‑derived factor (SDF)‑1α, interleukin (IL)‑6, IL‑1β and tumor necrosis factor (TNF)‑α were detected by ELISA analysis. Treatment with anagliptin decreased balloon injury‑induced neointima formation, compared with the injury group (P<0.01). Body weight and food consumption did not alter following treatment with anagliptin. Anagliptin caused an increase in the serum active GLP‑1 concentration, compared with the injury group. In addition, serum SDF‑1α was significantly decreased by treatment with anagliptin (P<0.001). Anagliptin altered the serum activity of IL‑6, IL‑1β and TNF‑α (P<0.01). The results of the present study demonstrated that anagliptin appeared to attenuate neointimal formation by inhibiting inflammatory cytokines and chemokines following balloon injury, and that treatment with a dipeptidyl peptidase 4 inhibitor may be useful for future preclinical studies and potentially for the inhibition of thrombosis formation following percutaneous coronary intervention.
本研究评价了阿那格列汀对 Sprague-Dawley 大鼠颈动脉损伤后内膜增生的影响。280-300g 的 Sprague-Dawley 大鼠采用 2F Fogarty 球囊血栓切除术导管损伤。大鼠分为损伤组（生理盐水）和阿那格列汀组（10mg/kg/天）。在左颈动脉造成血管损伤，28 天后评估新生内膜形成。采集左右颈动脉进行组织学评价，并通过 ELISA 分析检测血浆胰高血糖素样肽 1 受体（GLP-1）、基质细胞衍生因子（SDF）-1α、白细胞介素（IL）-6、IL-1β和肿瘤坏死因子（TNF）-α的活性。与损伤组相比，阿那格列汀治疗降低了球囊损伤诱导的新生内膜形成（P<0.01）。阿那格列汀治疗后体重和食物消耗没有改变。与损伤组相比，阿那格列汀治疗后血清活性 GLP-1 浓度增加。此外，阿那格列汀治疗显著降低了血清 SDF-1α（P<0.001）。阿那格列汀改变了血清中 IL-6、IL-1β和 TNF-α的活性（P<0.01）。本研究结果表明，阿那格列汀通过抑制球囊损伤后炎症细胞因子和趋化因子，可能减轻新生内膜形成，二肽基肽酶 4 抑制剂的治疗可能对未来的临床前研究有用，并且可能抑制经皮冠状动脉介入治疗后的血栓形成。
