摘要
目的探讨烟酰胺核糖(nicotinamide riboside,NR)对1型糖尿病(DM)大鼠心肌线粒体融合分裂的作用及其机制。方法利用链脲佐菌素(streptozotocin,STZ)诱导1型DM大鼠模型,随机分为4组:正常对照(Con)组,Con+NR组,DM组,DM+NR组。监测大鼠血糖和体质量变化,葡萄糖耐量试验(IPGTT)检测糖代谢情况,采用小动物超声评估大鼠心脏功能变化,TUNEL法检测心肌细胞凋亡,DHE染色检测心肌细胞ROS含量,透射电镜观察线粒体形态,Western blot法检测线粒体分裂、融合相关蛋白表达水平。结果与Con组相比,DM组大鼠的血糖、血脂明显升高,体质量减轻,心脏左室射血分数(left ventricular ejection fraction,LVEF)和左心室短轴缩短率(Left ventricular fractional shortening,LVFS)减低,心肌细胞凋亡增加,氧化应激增强,线粒体分裂增多,线粒体融合蛋白Opa1表达下调(P<0.05,P<0.01);与DM组相比,DM+NR组大鼠心脏LVEF改善,心肌细胞凋亡减少,氧化应激减少,线粒体融合增加,线粒体融合蛋白Opa1和Mfn2表达上调(P<0.05)。结论 NR可增加DM心肌融合蛋白Opa1与Mfn2的表达,抑制DM心肌线粒体分裂,降低DM心肌凋亡和氧化应激,改善心脏功能。
AIM To investigate the effect of nicotinamide riboside(NR) on mitochondrial fusion and fission in type 1 diabetic hearts and its underlying mechanisms.METHODS Type 1 diabetic mellitus(DM) rat models were induced by streptozotocin(STZ) injection.The animals were randomly divided into four groups:Control(Con) group,Con+NR group,DM group,and DM+NR group.Blood glucose and body weight were measured.Intraperitoneal glucose tolerance test(IPGTT) was used to determine glucose metabolism.Cardiac functions were evaluated by echocardiography,cardiomyocyte apoptosis was determined by TUNEL assay and ROS was detected by DHE staining.Mitochondrial morphology was analyzed by transmission electron microscope and plasma triglyceride(TG) and total cholesterol(TC) were detected by automatic biochemical analyzer.Western blot was used to detect the expressions of mitochondrial fission and fusion-related proteins.RESULTS Compared with those in control group,the blood glucose and blood lipid were significantly increased and the body weight was decreased in diabetic rats.Cardiac functions were impaired in diabetic rats(P<0.05,P<0.01) and the expression of Opa1 was significantly down-regulated(P<0.01).Cardiomyocyte apoptosis and oxidative stress were increased in diabetic hears and mitochondrial fission was significantly enhanced in diabetic hearts(P<0.01).NR treatment effectively improved cardiac functions in diabetic rats and reduced cardiomyocyte apoptosis and oxidative stress in diabetic hearts(P<0.05).Importantly,NR treatment increased Opa1 expression and promoted mitochondrial fusion in diabetic hearts(P<0.01).CONCLUSION Nicotine ribose increases the expression of Opa1 and prevents mitochondrial fission in diabetic hearts.Nicotine ribose inhibits cardiomyocyte apoptosis and oxidative stress and improves cardiac functions in diabetic rats.
作者
邱继欢
文和
胡朗
亓秉超
刘振华
常盼
李春雨
刘超阳
史睿
付锋
李妍
QIU Ji-huan;WEN He;HU Lang;QI Bing-chao;LIU Zhen-hua;CHANG Pan;LI Chun-yu;LIU Chao-yang;SHI Rui;FU Feng;LI Yan(Department of Cardiology,Tangdu Hospital,Air Force Medical University,Xi’an 710038,Shaanxi,China;Department of Physiology,School of Basic Medical Sciences,Air Force Medical University,Xi’an 710032,Shaanxi,China;Department of Life Science and Medicine,Northwestern University,Xi’an 710069,Shaanxi,China)
出处
《心脏杂志》
CAS
2020年第1期6-13,共8页
Chinese Heart Journal
基金
国家自然科学基金项目资助(81570252,81770369)
陕西省科技厅一般项目资助(2018SF-129)。
关键词
烟酰胺核糖
糖尿病心肌病
线粒体动力学
氧化应激
凋亡
Opa1
Nicotinamide ribose
Diabetic cardiomyopathy
Mitochondrial Dynamics
Oxidative stress
Apoptosis
Opa1
