Njerve Ida Unhammer, Åkra Sissel, Weiss Thomas W, Solheim Svein, Øvstebø Reidun, Aass Hans Christian D, Byrkjeland Rune, Arnesen Harald, Seljeflot Ingebjørg
Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway.
Center for Heart Failure Research, Oslo University Hospital Ullevaal, Oslo, Norway.
Mediators Inflamm. 2017;2017:5380638. doi: 10.1155/2017/5380638. Epub 2017 May 15.
Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM.
Patients ( = 12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at -150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR).
HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo ( = 0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group ( = 0.043, both), significantly different from that in the placebo ( = 0.009 and = 0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers.
In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies.
有关格列汀类药物潜在抗炎和抗动脉粥样硬化作用的研究已取得了有前景的结果。我们的目的是研究沙格列汀治疗是否会改变炎症标志物的表达，主要是在稳定型冠状动脉疾病（CAD）和2型糖尿病（T2DM）患者的外周血单核细胞（PBMC）和循环白细胞中。
将患者（n = 12）随机分为每日服用5mg沙格列汀组或安慰剂组，为期3个月。在研究开始时和结束时，于空腹状态且未服用药物前采集样本。分离PBMC并在-150°C下冷冻保存，直至离体后暴露于1ng/mL脂多糖（LPS）中4小时。使用定制设计的TaqMan®阵列进行基因表达分析，并通过实时PCR（RT-qPCR）进行相对定量。
与安慰剂组相比，沙格列汀治疗组的糖化血红蛋白（HbA1c）有所降低（P = 0.042）。在未刺激的PBMC和循环白细胞中，我们观察到沙格列汀组白细胞介素-10（IL-10）的表达显著增加（均为P = 0.043），与安慰剂组有显著差异（分别为P = 0.009和P = 0.032）。在所选择的任何促炎标志物中，未观察到组间变化的差异。
在我们这个由T2DM合并CAD患者组成的小队列中，本研究观察到的沙格列汀可能的抗炎作用，即通过上调白细胞中的IL-10来实现，需要在更大规模的研究中得到证实。
