西格列汀对Ⅱ型糖尿病大鼠骨髓内皮祖细胞衰老的影响及可能机制

目的:探讨西格列汀对Ⅱ型糖尿病大鼠骨髓内皮祖细胞(EPCs)衰老的影响及可能机制。方法:建立SD大鼠Ⅱ型糖尿病模型,成模大鼠随机分为模型组,西格列汀低、中、高剂量组(西格列汀组),西格列汀与烟酰胺联合用药组(西格列汀+烟酰胺组);正常大鼠随机分为正常对照组及烟酰胺组。每周测体质量及随机亦糖,ELISA检测血清中胰高血糖素样肽-1(GLP-1)和二肽基肽酶4(DPP-4)水平,β-半乳糖苷酶染色法检测EPCs的衰老阳性率,RT-qPCR检测EPCs中沉默信息调节因子1(SIRT1)的mRNA表达水平。结果:烟酰胺组与对照组相比,EPCs衰老阳性率明显降低;DM组与NC组比较显示成模后大鼠血清DPP-4水平升高、GLP-1水平下降,EPCs中SIRT1 mRNA相对表达量下调,EPCs衰老阳性率上升,差异均有统计学意义;成模大鼠在西格列汀干预后,随着药物剂量增加,与模型组比较,大鼠血清中DPP-4水平下降、GLP-1水平升高,EPCs中SIRT1 mRNA相对表达量上调,EPCs衰老阳性率呈现下降趋势,差异均有统计学意义;与高剂量西格列汀组相比,西格列汀+烟酰胺组大鼠EPCs衰老阳性率升高,差异有统计学意义。结论:西格列汀能缓解Ⅱ型糖尿病大鼠EPCs衰老,其作用机制可能涉及SIRT1介导的DPP-4/GLP-1通路。

Effect of sitagliptin on senescence of endothelial progenitor cells of bone marrow in type 2 diabetes mellitus rats and its possible mechanism

Objective:To study the effect of sitagliptin on senescence of endothelial progenitor cells (EPCs) of bone marrow in type 2 diabetes mellitus rat and its possible mechanism.Methods:Type 2 diabetes mellitus rat model was induced by high amounts of sugar and fat chow combined with single injection of streptozotocin (35 mg · kg-1).After the model was established,type 2 diabetes mellitus rats were randomly divided into model (DM)group,seitagliptin injection group and seitagliptin combined with nicotinamide injection (seitagliptin+NAM) group.Normal rats were randomly divided into normal control (NC) group and nicotinamide injection (NAM) group.The weight and blood glucose of rats in all groups were detected each week.The DM and NC groups were received physiologic saline administration and the treatment groups with seitagliptin or NAM for 4 weeks.The level of dipeptidyl deptidase-4 (DPP-4) and glucagon like peptide-1 (GLP-1) in plasma were measured by ELISA,the percentage of senescenced EPCs from bone marrow and the mRNA expression of SIRT1 were measured by RT qPCR.Results:Compared with the NC group,the percentage of senescenced EPCs in the NAM group reduced significantly (P＜0.05).The level of DPP-4 and GLP-1 in plasma and the mRNA expression of SIRT1 showed no significant difference between the NC group and NAM group.Compared with the NC group,the level of DPP-4 in plasma and the percentage of senescenced EPCs from bone marrow increased.The level of GLP-1 in plasma and the mRNA expression of SIRT1 in EPCs decreased in DM group,and showed significant difference between the NC and DM group.Compared with the DM group,the level of DPP-4 in plasma and the percentage of senescenced EPCs from bone marrow decreased.The level of GLP-1 in plasma and the mRNA expression of SIRT1 in EPCs increased in seitagliptin group in a dose-dependent manner,which had a significant difference between the DM and seitagliptin group.Compared with the sitagliptin (30 mg · kg-1) group,the percentage of senescenced EPCs from bone marrow increased in sitagliptin+NAM group,which had a significant difference between the sitagliptin and sitagliptin+ NAM group.Conclusion:Seitagliptin reduces senescence of EPCs in type 2 diabetic rats which may involve in the SIRT1/DPP-4/GLP-1 pathway.