四氢生物蝶呤对糖尿病小鼠心肌损伤的保护作用

Protective effect of tetrahydrobiopterin on myocardium injury in db/db mice

摘要:

目的：研究四氢生物蝶呤（Tetrahydrobiopterin，BH4）对db/db糖尿病小鼠心肌中氧化应激的影响及其可能机制。方法：给予糖尿病模型db/db小鼠磷酸盐缓冲液（Phosphate buffer solution，PBS），低剂量BH4[10 mg/（kg·d）]、高剂量BH4[50 mg/（kg·d）]干预8周，并以C57小鼠为正常对照组，检测心功能指标，检测心肌组织H2O2水平、丙二醛（Malondialdehyde，MDA）含量和超氧化物歧化酶（Superoxide dismutase，SOD）活性。结果：糖尿病组心功能指标明显降低，心肌内H2O2水平明显增加，MDA含量增加，而SOD活性没有明显降低；而不同剂量的BH4能改善心功能指标，降低心肌组织内H2O2水平和MDA含量，并明显提高SOD活性。结论：BH4可以提高糖尿病小鼠心脏功能，降低心肌内氧化应激状态，提高抗氧化能力，提示改善氧化应激可能是BH4改善糖尿病心肌病的机制之一。

Abstract:

Objective：To investigate the effect of the tetrahydrobiopterin，which is known to be an important cofactor of nitric oxide synthase（NOS） and an antioxidant，on development of diabetic cardiomyopathy in db/db mice and the underlying mechanism. Methods：Db/db mice were treated with phosphate buffer solution（PBS），low dosage tetrahydrobiopterin（BH4） [10 mg/（kg·d）] or high dosage BH4[50 mg/（kg·d）] for 8 weeks by gavages. C57 mice were used as normal control. Cardiac function was measured by inserting a Millar catheter into the left ventricle. Then，myocardial H2O2 level，malondialdehyde（MDA） level and superoxide dismutase（SOD） activity were detected in every group. Results：The cardiac function in diabetic group was significantly suppressed compared with that in normal control group. Meanwhile，compared with those in normal control group，H2O2 and MDA in diabetic group were both increased. However，no difference was observed in SOD activity between normal control group and diabetic group. After treatment of BH4，the cardiac function was improved in both low dosage and high dosage BH4 groups than in diabetic group. In addition，treatment with BH4 attenuated the H2O2 and MDA levels and increased the SOD activity. Conclusion：The data suggest that BH4 can significantly improve cardiac function of db/db diabetic mice，attenuate the oxidative stress and improve antioxidant capacity.