甲状腺激素下调慢性心力衰竭大鼠心肌钙调神经磷酸酶通路的机制研究  

Mechanism study of thyroid hormone down-regulating myocardial calcineurin pathway in rats with chronic heart failure

作　　者：邝素华[1] 郭锻强[2] 梁庆[2] 马伦超[1] 杨超[1] 陆国梁[1] 张英元[1] 黄杰周[1] 翁丽芳[1] 任晓山[1] 谢少波[1] KUANG Su-hua GUO Duan-qiang LIANG Qing MA Lun-chao YANG Chao LU Guo-liang ZHANG Ying-yuan HUANG Jie-zhou WENG Li-fang REN Xiao-shan XIE Shao-bo(Department of Cardiac Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China Department of Emergency Medicine , The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China)

机构地区：[1]广州医科大学附属第一医院心脏外科,广州510120 [2]广州医科大学附属第一医院急诊科,广州510120

出　　处：《岭南心血管病杂志》2017年第3期314-318,346,共6页South China Journal of Cardiovascular Diseases

基　　金：广东省医学科研基金(项目编号:A2014287);广州市医药卫生科技项目(项目编号:20141A011077);广州市医药卫生科技项目(项目编号:20151A011069)

摘　　要：目的在体研究甲状腺素(thyroid hormone,TH)对慢性心力衰竭(heart failure,HF)大鼠血流动力学及心脏Ca^(2+)-调神经磷酸酶(calcineurin,CaN)-T细胞核因子3(nuclear factor 3 of activated T cells,NFAT3)通路的影响。方法 SD大鼠90只随机分为3组,各组30只:(1)假手术组(sham组);(2)HF模型组(HF组);(3)TH治疗组(TH组)。缩窄腹主动脉建立HF动物模型,TH组术后灌胃予左甲状腺素钠[1.5μg/(100 g·d)]。各组大鼠喂养8周后测定有创血流动力学指标,取材称量全心湿质量(heart wet weight,HW)、全肺湿质量(lung weight,LW),计算心质量指数[HW/体质量(body weight,BW)]、肺质量指数(LW/BW),测定心肌[Ca^(2+)]i浓度及CaN活性,Western blot检测CaN-A、总NFAT3(T-NFAT3)、磷酸化NFAT3(P-NFAT3)蛋白表达水平。结果(1)TH治疗显著改善HF大鼠收缩压(systolic pressure,SP)、左心室收缩压(left intraventricular systolic pressure,LVSP)、+dp/dt max、左心室舒张压(left ventricular diastolic pressure,LVDP)、左心室舒张末期压力(left ventricular end-diastolic pressure,LVEDP)、-dp/dt max;TH组与HF组心率比较,差异无统计学意义(P>0.05)。(2)TH组HW/BW[(3.44±0.27)mg/g vs.(4.18±0.28)mg/g,P<0.01]及LW/BW[(8.02±0.41)mg/g vs.(8.56±0.45)mg/g,P<0.01]均较HF组有所降低,差异有统计学意义。(3)与HF组比较,TH组大鼠[Ca^(2+)]i[(115.50±10.76)nmol/L vs.(159.36±7.21)nmol/L,P<0.01]及CaN活性[(21.33±2.35)nmol·min^(-1)·mg^(-1)protein vs.(42.96±3.36)nmol·min^(-1)·mg^(-1)protein,P<0.05]均显著降低。(4)HF组P-NFAT3表达(0.41±0.10 vs.0.80±0.11,P<0.01)及P-NFAT3/T-NFAT3比值(0.13±0.03 vs.0.25±0.04,P<0.01)较Sham组显著减少,差异有统计学意义;TH组P-NFAT3表达(0.86±0.11vs.0.41±0.10,P<0.01)及P-NFAT3/T-NFAT3比值(0.27±0.03 vs.0.13±0.03,P<0.01)较HF组则显著增加,差异有统计学意义;虽TH组P-NFAT3表达较Sham组有所增加,而TH组P-NFAT3/T-NFAT3比值与Sham组比较,差异无统计学意义(P=0.193)。结论 TH通过改善心肌钙稳态,减少对CaObjectives To explore the in vivo study of the thyroxine effect on hemodynamics and cardiac calcineurin（Ca N）-nuclear factor 3 of activated T cells（NFAT3）pathway in chronic heart failure rats. Methods A total of 90 Sprague-Dawley rats were randomly divided into 3 groups,30 rats in each group：（1）sham group;（2）heart failure（HF）group（HF group）;（3）thyroid hormone（TH）treated group（TH group）. HF group and TH treated group rats were subject to abdominal aortic ligation,and TH group rats received intragastric administration of levothyroxine sodium [1.5 μg/（100 g · d）]. Invasive hemodynamic examination was performed before rats being sacrificed and after eight weeks. Heart wet weight（HW）,lung wet weight（LW）,heart weight index[HW/body weight（BW）]and pulmonary weight index（LW/BW）were calculated. Myocardial[Ca^2＋]i concentration and CaN activity were measured,and CaN-A,total NFAT3（T-NFAT3）,phosphated-NFAT3（P-NFAT3）protein expression level were detected by Western blotting. Results（1）TH treatment significantly improved systolic pressure（SP）,left intraventricular systolic pressure（LVSP）,＋dp/dt max,left ventricular diastolic pressure（LVDP）,left ventricular end-diastolic pressure（LVEDP）,-dp/dt max in HF rats,and there were no statistical difference between TH group＇s HR and HF group＇s（P〉0.05）.（2）TH group＇s HW/BW[（3.44±0.27）mg/g vs.（4.18±0.28）mg/g,P〈0.01]and LW/BW[（8.02±0.41）mg/g vs.（8.56±0.45）mg/g,P〈0.01]were significantly lower than HF group＇s.（3）Compared with HF group＇ s,TH group＇ s[Ca^2＋]i[（115.50 ± 10.76）nmol/L vs.（159.36 ± 7.21）nmol/L,P〈0.01]and CaN activity[（21.33±2.35）nmol·min^-1﹒mg^-1protein vs.（42.96±3.36）nmol·min^-1·mg^-1protein,P〈0.05]were significantly lower.（4）Caompared with those of sham group,expression level of P-NFAT3（0.41±0.10 vs. 0.80±0.11,P〈0.01） and PNFAT3/T-NFAT3 ratio（0.13±0.03 vs. 0.25±0.04,P〈0.01） in HF group were

关 键 词：心力衰竭 甲状腺激素 钙调神经磷酸酶 钙调控 心肌质量构 

分 类 号：R541.6[医药卫生—心血管疾病]