1型糖尿病大鼠骨髓内皮祖细胞衰老与非对称二甲基精氨酸浓度升高有关

Involvement of Asymmetric Dimethylarginine in Senescence of Endothelial Progenitor Cells from Type 1 Diabetes Mellitus Rat Bone Marrow

目的研究非对称二甲基精氨酸与1型糖尿病大鼠骨髓内皮祖细胞衰老之间的关系。方法单次腹腔注射链脲佐菌素(65 mg/kg)建立1型糖尿病大鼠模型,检测血糖、骨髓内皮祖细胞衰老、血浆非对称二甲基精氨酸水平以及内皮祖细胞中二甲基精氨酸-二甲胺水解酶2和SIRT1的mRNA表达。结果与对照组比较,糖尿病大鼠血浆非对称二甲基精氨酸水平显著升高(0.67±0.06μmol/L比0.55±0.07μmol/L)、内皮祖细胞衰老率增加(39%±8%比11%±2%)、二甲基精氨酸-二甲胺水解酶(0.56±0.17比1.00±0.22)和SIRT1(0.08±0.17比1.00±0.39)的mRNA表达下调。结论糖尿病大鼠内皮祖细胞衰老与非对称二甲基精氨酸水平升高有关,其机制可能涉及SIRT1/二甲基精氨酸-二甲胺水解酶2途径。

Aim To explore the relationship of asymmetric dimethylarginine（ADMA）and senescence of endothelial progenitor cells（EPC） in type 1 diabetic rats.Methods The rat model of type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin（STZ,65 mg/kg） for one time.The concentration of fasting blood glucose,the level of ADMA in plasma,the percentage of senescence of EPC from bone marrow and the mRNA expression of dimethylarginine dimethylaminohydrolase 2（DDAH2） and SIRT1 were detected.Results The senescence percentage of EPC（39 % ± 8 % vs 11 %±2%） and the level of ADMA（0.67± 0.06 μmol/L vs 0.55± 0.07 μmol/L）in plasma were increased and the expression of DDAH2 and SIRT1 mRNA were down-regulated（0.56 ± 0.17 vs 1.00 ± 0.22,0.08 ± 0.17 vs 1.00 ± 0.39）.Conclusion The senescence of EPC was related with the increased level of ADMA in plasma,which may involve the SIRT1/DDAH2 pathway.