烟酰胺核糖抵抗高脂饮食诱导心肌损伤的机制研究  

Study on the mechanism of nicotinamide riboside improving high fat diet-induced myocardial injury

作　　者：郭艳杰 文和 卫锦娟 王莹 倪四峰 马炜 王长鹰 陈宁 GUO Yanjie;WEN He;WEI Jinjuan;WANG Ying;NI Sifeng;MA Wei;WANG Changying;CHEN Ning(Department of Cardiology,Xi’an International Medical Center Hospital,Xi’an 710075,China;School of Aerospace Medicine,Fourth Military Medical University;Department of Cardiology,Tangdu Hospital,Air Force Medical University;Northwest A&F University Hospital)

机构地区：[1]西安国际医学中心医院心内科,西安710075 [2]空军军医大学航空航天医学系 [3]空军军医大学唐都医院心内科 [4]西北农林科技大学医院

出　　处：《山西医科大学学报》2021年第10期1299-1304,共6页Journal of Shanxi Medical University

基　　金：国家自然科学基金青年项目(81800229)。

摘　　要：目的明确烟酰胺核糖(nicotinamide riboside,NR)抑制高脂诱导心肌损伤的治疗作用及其具体机制。方法将8周龄小鼠随机分为正常饮食组(Con组)、高脂饮食组(high fat diet,HFD组)和治疗组(HFD+NR组),Con组采用常规饮食喂养,HFD组给予高脂饮食喂养4个月。HFD+NR组给予高脂喂养4个月,在高脂喂养第3月初开始以800 mg/kg的烟酰胺核糖溶于生理盐水灌胃2个月。采用超声检测小鼠心脏左室射血分数和左室短轴缩短率。油红O染色检测心肌组织脂质含量,神经酰胺、游离脂肪酸、过氧化脂质含量检测试剂盒分别检测心肌组织神经酰胺、游离脂肪酸和过氧化脂质含量。用高脂培养基(500μmol/L palmitate棕榈酸,Pal)培养原代心肌细胞诱导高脂心肌损伤细胞模型。将大鼠乳鼠原代心肌细胞分为正常培养组(Con组)、高脂培养组(Pal组)和高脂培养+烟酰胺核糖组(Pal+NR组)。Con组使用正常培养基(DMEM高糖+10%胎牛血清+1%双抗),Pal组在Con组基础上给予500μmol/L的棕榈酸培养24 h;Pal+NR组在Pal组基础上加入2 mmol/L的烟酰胺核糖培养24 h。用Seahorse细胞能量代谢检测仪联合依托莫西检测原代心肌细胞外源性脂质相关的氧耗效率。用脂肪酸红色荧光探针(Bodipy 558/568 C12,Thermo公司)和线粒体绿色荧光探针(Mito-tracker green,Thermo公司)检测原代心肌细胞中脂肪酸和线粒体的分布。结果与Con组相比,HFD组小鼠心脏左心室射血分数和左心室短轴缩短率显著下降(P<0.05),心肌组织脂滴、神经酰胺、游离脂肪酸和过氧化脂质含量显著升高(P<0.05)。与HFD组相比,HFD+NR组小鼠心脏功能显著改善,心肌组织脂滴、神经酰胺、游离脂肪酸和过氧化脂质含量显著下降(P<0.05)。Seahorse检测原代心肌细胞脂代谢水平结果显示,相比于Pal组原代心肌细胞,Pal+NR组原代心肌细胞脂代谢相关的基础氧耗率和最大氧耗率均显著升高(P<0.05)。与正常培养组(ConObjective To clarify the therapeutic effect of nicotinamide riboside(NR)on myocardial injury induced by high fat diet and its underlying mechanism.Methods Eight-week-old C57 mice were divided into normal diet group(Con),high fat diet group(HFD)and treatment group(HFD+NR).The mice were fed with a regular diet in Con group,and the mice were fed with a high fat diet for 4 months in HFD group.The mice in HFD+NR group were given high fat for four months and NR solution gavage at a dose of 800 mg/kg for two months from the third month.Left ventricular ejection fraction(LVEF)and left ventricle fractional shortening(LVFS)were detected by ultrasound.Oil red O staining was used to detect the lipid content in myocardium.Ceramide,free fatty acid,and lipid peroxide content detection kits were used to detect the contents of ceramide,free fatty acid and lipid peroxide.Primary cardiomyocytes were divided into normal group(Con),high fat group(Pal)and high fat+nicotinamide ribose group(Pal+NR).Primary cardiomyocytes in Con group were cultured in normal medium(DMEM high glucose+10%fetal bovine serum+1%double antibody).Primary cardiomyocytes in Pal group were given 500μmol/L palmitic acid for 24 h on the basis of Con group.Primary cardiomyocytes in Pal+NR group were added 2 mmol/L NR on the basis of Pal group.Seahorse XF analyzer combined with Etomoxir were used to detect the level of lipid metabolism.Fatty acid red fluorescent probe(Bodipy 558/568 C12,Thermo)and mitochondrial green fluorescent probe(Mito-tracker green)were used to detect the distribution of fatty acids and mitochondria in primary cardiomyocytes.Results Compared with Con group,the left ventricular ejection fraction and the left ventricular short axis shortening rate in HFD group were significantly decreased(P<0.05),while myocardial tissue lipid droplets,ceramide,free fatty acid and peroxide lipid content were significantly increased(P<0.05).Compared with HFD group,cardiac LVEF and LVFS of the mice were significantly improved in HFD+NR group(P<0.05),and the contents

关 键 词：烟酰胺核糖 高脂饮食 脂毒性 脂肪酸氧化 线粒体 

分 类 号：R363[医药卫生—病理学]