随意跑轮运动对糖尿病大鼠心肌NADPH氧化酶及心脏重塑的影响

Effects of voluntary wheel running on the expression of nicotinamide-adenine dinucleotide phosphate oxidase and cardiac remodeling of the myocardium in diabetes

目的:观察随意跑轮运动对糖尿病大鼠心肌烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶调节亚基p47 phox及p67 phox表达的影响,初步探讨运动训练抑制糖尿病心脏氧化应激及心脏重塑的可能机制。方法:采用随机数字表法将40只SD大鼠分为正常对照组、模型组及运动组,后2组采用链脲佐菌素进行糖尿病造模。于造模成功1周后正常对照组及模型组大鼠均置于鼠笼内安静饲养,运动组大鼠给予8周(5 d/周)随意跑轮运动。于末次训练结束48 h后取静脉血测定血糖含量,利用超声心动图检测心脏结构及功能,采用Masson染色进行心肌组织病理学观察并检测心肌纤维化指数,将心肌组织匀浆后测定丙二醛(MDA)及活性氧(ROS)含量,采用Western blot技术检测心脏NADPH氧化酶p47 phox及p67 phox亚基蛋白表达量。结果:与正常对照组比较,模型组血糖含量升高(P<0.05),左心室收缩末期直径(LVESD)和左心室舒张末期直径(LVEDD)增加(P<0.05),左心室射血分数(LVEF)下降(P<0.05),心肌纤维化指数增加(P<0.05),MDA及ROS含量升高(P<0.05),p47 phox及p67 phox亚基蛋白表达量上调(P<0.05);与模型组比较,运动组血糖含量降低(P<0.05),LVESD及LVEDD下降(P<0.05),LVEF升高(P<0.05),心肌纤维化指数降低(P<0.05),MDA及ROS含量下降(P<0.05),p47 phox及p67 phox亚基蛋白表达量下调(P<0.05)。结论:随意跑轮运动能通过抑制NADPH氧化酶调节亚基p47 phox及p67 phox表达,减轻糖尿病大鼠心脏氧化应激反应,进而抑制心脏重塑并增强心功能。

Objective To explore the effect of voluntary wheel running on the expression of the p47phox and p67phox regulatory subunits of nicotinamide-adenine dinucleotide phosphate(NADPH)oxidase in the myocardia of diabetic rats,and possible molecular mechanisms by which exercise suppresses oxidative stress and improves cardiac remodeling in diabetic cardiomyopathy.Methods Forty 8-week-old healthy male Sprague-Dawley rats were randomly divided into a normal control group(NC),a diabetes mellitus sedentary group(DM-Sed)and a diabetes mellitus exercise training group(DM-ExT).A model of diabetes was induced by feeding streptozotocin to the latter two groups.After successful modelling,the animals in the NC and DM-Sed groups were raised quietly in their cages,while the DM-ExT group performed voluntary wheel running 5 days/week for eight weeks.Forty-eight hours after the last running,venous blood samples were taken to determine the content of blood glucose.Cardiac structure and function were detected by echocardiography,and Masson staining and myocardial histopathology generated a myocardial fibrosis index.The rats were sacrified and malondialdehyde(MDA)and reactive oxygen species(ROS)were measured in their myocardial tissue.The expression of NADPH oxidase′s p47phox and p67phox subunit proteins was quantified using western blotting.Results Compared with the NC group,the average content of blood glucose,MDA and ROS had increased significantly in the DM-Sed group.The average end-systolic and end-diastolic diameter of the left ventricle had also increased significantly,as had the myocardial fibrosis index,and the expression of the p47phox and p67phox subunit proteins.The average left ventricular ejection fraction had decreased significantly.Compared with the DM-Sed group,the average blood glucose,MDA and ROS levels in the DM-ExT group were significantly lower.The average end-systolic and end-diastolic diameter of the left ventricle were also smaller,and the myocardial fibrosis index and the p47phox and p67phox subunit protein concentrations were significantly lower as well.Conclusions Voluntary wheel running can attenuate oxidative stress on the heart in rats modeling diabetes by inhibiting the expression of NADPH oxidase regulatory subunits p47phox and p67phox,thus improving cardiac remodeling and enhancing cardiac function.