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过表达髓样分化蛋白1对高脂饮食诱导的肥胖小鼠心电的影响

Effect of overexpression of myeloid differentiation protein 1 on electrophysiology in obese mice induced by high fat diet
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摘要 目的研究髓样分化蛋白1(MD1)对高脂饮食诱导的肥胖小鼠心电的影响。方法野生型(WT)和转基因的MD1过表达(TG)的小鼠各24只,分别将野生型和转基因型小鼠随机分两组,每组12只,普通饮食的野生型小鼠组(WT-ND)和普通饮食的MD1转基因小鼠组(TG-ND)给予普通饮食,高脂饮食的野生型小鼠组(WT-HFD)和高脂饮食的MD1转基因小鼠组(TG-HFD)给予高脂饮食。普通饮食和高脂饮食分别喂养20 W后,测定四组的腹腔注射葡萄糖后0、15、60和120 min的血糖值,测量血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)。随后心脏超声测定心脏左室缩短分数(LVFS)、左室收缩期末内径(LVESD)、左室舒张期末内径(LVEDD)等心功能指标。Ⅱ导联记录小鼠体表心电图,测量或计算心电图的RR间期、QT间期和QTc间期。心脏离体Langendorff灌流,通过S1S1(起搏周长从150 ms逐渐递减至30 ms)刺激测量心室单相动作电位交替阈值(ALT)和90%动作电位时程(APD90),通过S1S2(S1S1150 ms,S1S2从120 ms逐渐递减至30 ms)刺激测量心室有效不应期(VERP),通过Burst刺激测量室性心律失常诱发率来评估心室电重构。结果四组小鼠基础体重无差异,高脂饮食喂养第12周时,WT-HFD组比WT-ND组体重增加明显,以及TG-HFD组比TG-ND组体重增加明显。与WT-ND组相比较,WT-HFD组糖耐量降低,而TG-HFD组与WT-HFD组相比较,TG-HFD组糖耐量增加。与普食组相比,高脂组血脂指标(TC、TG、LDL)明显升高。与WT-ND组相比,WT-HFD组LVESD增大,而TG-HFD组与WT-HFD组相比,TG-HFD组LVESD减小。与WT-ND组相比较,WT-HFD组QTc间期明显延长[(54.1±2.1)ms vs(42.4±1.4)ms,P<0.05],APD90明显延长[PCL150 ms,(71.6±4.7)ms vs(53.9±3.8)ms,P<0.05],心室的有效不应期缩短[(37.8±4.3)ms vs(48.2±4.4)ms,P<0.05],诱发心室电交替最大起搏周长增加[(112.8±8.0)ms vs(70.6±8.5)ms,P<0.05]。与WT-HFD组比较,TG-HFD组QTc间期缩短[(48.3±1.1)ms vs(54.1±2.1)ms,P<0.05],APD90缩短[(61.6±3.1)ms vs(71.6±4.7)ms,P<0.05],心室有效不应期延长[(47.5±3.3)ms vs(37.8±4.3)ms,P<0.05],诱发心室电交替最大起搏周长缩短[(83.8±6.9)ms vs(112.8±8.0)ms,P<0.05]。结论过表达MD1可以改善高脂饮食诱导的糖代谢紊乱,并且降低室性心律失常发生的风险。 Objective To investigate the effect of myeloid differentiation protein 1(MD1)on electrophysiology in obese mice induced by high fat diet.Methods Wild type(WT)and transgenic mice with MD1 overexpression(TG)were randomly divided into two groups with 12 mice in each group.Wild-type mice on a normal diet(WT-ND)and MD1 transgenic mice on a normal diet(TG-ND)were given a normal diet,wild-type mice on a high-fat diet(WT-HFD)and high-fat mice on a high-fat diet(TG-HFD)were given a high-fat diet.After feeding the normal diet and high-fat diet for 20 W,respectively,blood glucose values of the four groups were measured at 0,15,60 and 120 min after intraperitoneal injection of glucose,followed by cardiac ultrasound measurement of cardiac function indexes such as left ventricular fractional shortening(LVFS),left ventricular end-systolic dimension(LVESD)and left ventricular end-diastolic dimension(LVEDD).Serum total cholesterol(TC),triglyceride(TG),and low density lipoprotein(LDL)were measured.LeadⅡwas used to record the surface ECG of mice,and the RR interval,QT interval and QTc interval were measured.In vitro cardiac Langendorff perfusion,alternating threshold of ventricular monophasic action potential(ALT)and 90%action potential time history(APD90)were measured by S1S1 stimulation(PCL decline gradually from 150 ms to 30 ms),ventricular effective refractive period(VERP)was measured by S1S2 stimulation(S1 S2150 ms,S1S2 decline gradually from 120 ms to 30 ms),and ventricular arrhythmia induction rate were measured by Burst stimulation to evaluate ventricular electrical remodeling.Results There was no difference in the basal weight of the four groups.At the 12 th week of high-fat diet,the WT-HFD gained significantly more weight than the WT-ND,and the TG-HFD gained significantly more weight than the TG-ND.Compared with the WT-ND,the glucose tolerance of the WT-HFD decreased,while the TG-HFD had an increased glucose tolerance compared with the WT-HFD.Compared with the general diet group,the blood lipids(TC,TG,LDL)in the high-fat group were significantly increased.Compared with the WT-ND group,the LVESD in the WT-HFD group was increased,while the LVESD in the TG-HFD group was decreased compared with the WT-HFD group.Compared with WT-ND,WT-HFD had significantly longer QTc interval[(54.1±2.1)ms vs(42.4±1.4)ms,P<0.05]and APD90 significantly longer[PCL150 ms,(71.6±4.7)ms vs(53.9±3.8)ms,P<0.05],and shorter effective refractory period[(37.8±4.3)ms vs(48.2±4.4)ms,P<0.05].Compared with WT-HFD,TG-HFD had shorter QTc interval[(48.3±1.1)ms vs(54.1±2.1)ms,P<0.05],shorter APD90[(61.6±3.1)ms vs(71.6±4.7)ms,P<0.05],prolonged ventricular effective refractory period[(47.5±3.3)ms vs(37.8±4.3)ms,P<0.05],and shortened induction of ventricular alternating maximum paced cycle length[(83.8±6.9)ms vs(112.8±8.0)ms,P<0.05].Conclusions Overexpression of MD1 can ameliorate glucose metabolism disorders and reduce the risk of ventricular arrhythmias induced by high-fat diets.[Chinese Journal of Cardiac Pacing and Electrophysiology,2020,34(1):37-43]
作者 付辉 帅维 孔彬 沈才杰 蒋小波 黄鹤 FU Hui;SHUAI Wei;KONG Bin;SHEN Cai-jie;JIANG Xiao-bo;HUANG He(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Rsearch Institute,Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China)
出处 《中国心脏起搏与心电生理杂志》 2020年第1期37-43,共7页 Chinese Journal of Cardiac Pacing and Electrophysiology
基金 国家自然科学基金(No.81570306).
关键词 心血管病学 髓样分化蛋白1 高脂饮食 Langendorff灌流 心室电重构 Cardiology Myeloid differentiation protein 1 High fat diet Langendorff perfusion Ventricular electrical remodeling
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