烟酰胺核糖抑制db/db小鼠糖尿病心肌病的作用及机制研究

目的:探讨烟酰胺核糖(NR)对2型糖尿病小鼠心肌病的治疗作用及其机制。方法:2型糖尿病模型db/db鼠和及其严格对照小鼠db/+小鼠,将小鼠分为Con (db/+)组,DM (db/db)组,DM+NR组。采用超声测小鼠心脏功能,western-blot及免疫组化测SIRT1表达含量,DHE染色、MDA含量和MnSOD活性检测反映氧化应激水平。结果:与对照组相比,db/db小鼠心脏功能显著下降(LVEF:42.3±7.2vs 73.7±10.2, P0.01;LVFS:22.1±4.2vs 42.7±6.9, P0.01),SIRT1表达量显著下调(P0.01)。NR喂养提高SIRT1表达量(P0.01),并有效改善db/db小鼠心脏功能(LVEF:53.1±8.1vs 42.3±7.2, P0.01;LVFS:33.4±6.9vs 22.1±4.2, P0.01)。同时,NR喂养显著降低了db/db小鼠心肌组织的凋亡水平和氧化应激水平(P0.05)。结论:NR有效改善了db/db小鼠的心功能障碍,降低了db/db小鼠的心肌凋亡水平和氧化应激水平,这些作用的发挥可能与NR增加SIRT1的表达量有关。

Study on Effect and Mechanism of Nicotinamide Ribose Inhibiting Diabetic Cardiomyopathy in db/db Mice

ABSTRACT Objective: To clarify the therapeutic effect of nicotinamide ribose (NR) on type 2 diabetic myocardial injury in mice and its potential underlying mechanism. Methods: Type 2 diabetes model mice db/db mice and wild C57 mice were purchased at 8 weeks old. The mice were divided into Con(db/+) group, DM (db/db) group and DM+NR (db/db+NR) group. Echocardiology was used to mea- sure the heart function of mice. The expression of SIRT1 was detected by western-blot and immunohistochemistry. ROS level, MDA content and MnSOD activity was detected to reflect oxidative stress level. Results: Compared with the control group, the cardiac function of db/db mice decreased significantly (LVEF: 42.3±7.2vs 73.7±10.2, P<0.01; LVFS: 22.1±4.2vs 42.7±6.9, P<0.01), and the expres- sion of SIRT1 was significantly down-regulated (P<0.01). NR feeding increased SIRT1 expression (P<0.01) and effectively improved cardiac function in diabetic db/db mice (LVEF: 53.1±8.1vs 42.3±7.2, P<0.01; LVFS: 33.4±6.9vs 22.1±4.2, P<0.01). At the same time, NR feeding effectively reduced the level of apoptosis and oxidative stress in myocardial tissue of diabetic db/db mice (P<0.01). Conclusion: NR effectively improved cardiac dysfunction, reduced myocardial apoptosis and oxidative stress levels in diabetic db/db mice, and these effects may be exerted by the increased expression level of SIRT1 by NR.