Notch和核因子-κB信号通路在心肌梗死大鼠心肌细胞中的表达变化  

Expression changes of Notch and nuclear factor-κB signaling pathways in the rat heart withmyocardial infarction

作　　者：晋金兰 邓哲彤 吕荣贵[4] 刘喜鸿 韦建瑞 

机构地区：[1]广州市红十字会医院暨南大学医学院附属广州红十字会医院重症医学科,510220 [2]广州市红十字会医院暨南大学医学院附属广州红十字会医院超声科,510220 [3]广州市红十字会医院暨南大学医学院附属广州红十字会医院心血管内科,510220 [4]南方医科大学深圳医院心血管内科

出　　处：《中华心血管病杂志》2017年第6期507-512,共6页Chinese Journal of Cardiology

摘　　要：目的探讨Notch和核因子（NF）-κB信号通路在心肌梗死（心梗）大鼠心肌细胞中的表达变化。方法成年Sprague Dawley大鼠70只，雄性，平均体重（2504-20）g，随机数表法分为心梗组和对照组。采用结扎冠状动脉左前降支的方法建立大鼠心梗模型，即为心梗组。对照组大鼠仅接受冠状动脉左前降支血管下穿线而不结扎。将术后24h存活的两组大鼠再采用随机数表法分别分为3个亚组，即术后1周、4周和8周组，每亚组6只大鼠。取各组大鼠心脏非心梗区心肌组织，采用实时定量PCR法检测心肌细胞Notch信号受体Notchl、配体D114和下游靶基因HeslmRNA的表达水平，采用Westernblot法检测心肌细胞Notchl信号可溶性胞内片段NICDl蛋白的表达水平，采用试剂盒检测心肌细胞核内p65蛋白含量以反映心肌细胞NF-κB信号通路的活化情况。结果（1）各组大鼠心肌细胞Notch信号通路组成成分mRNA的表达：心梗组术后1周亚组大鼠非梗死区心肌细胞NotchlmRNA的表达水平明显高于对照组术后1周亚组（P〈0．05），而术后4周和8周亚组虽均高于对照组相应亚组，但差异均无统计学意义。心梗组术后1周、4周和8周亚组大鼠非梗死区心肌细胞Notch信号配体D114mRNA的表达水平以及Notch信号靶基因HeslmRNA的表达水平与对照组相应亚组比较差异均无统计学意义。（2）各组大鼠心肌细胞NICDl蛋白的表达：心梗组术后1周亚组大鼠非梗死区心肌细胞NICDl蛋白表达水平明显高于对照组术后1周亚组（P〈0．05），而术后4周和8周亚组虽均高于对照组相应亚组，但差异均无统计学意义。（3）各组大鼠心肌细胞NF-κB信号的活化情况：心梗组术后1周、4周和8周亚组大鼠非梗死区心肌细胞核内p65蛋白表达水平均明显高于对照组相应亚组（P分别〈0．01、0．01和0．05），其中以术后1周亚组为最高。结论Notch和NF．KB信号通路Objective To observe the expression changes of Notch and nuclear factor-KB （NF-KB） signaling pathways in rat myocardium post myocardial infarction. Methods Myocardial infarction was established by ligation of the left anterior descending coronary artery（ MI group）, sham rats （similar surgical procedure without coronary artery ligation） served as control, the rats were sacrificed at first week,4th and 8th week after operation, the non-infarct myocardial tissue in both groups was obtained to detect the mRNA expression of Notchl, Dl14 and Hesl by RT-PCR, the protein expression of NICD1 was detected by Western blot, the nuclear protein p65 content was detected to reflect the activation degree of NF-KB signaling in the cardiomyocytes. Results The myocardial mRNA expression of Notchl in MI group was significantly higher than in control group （ 1.68 ± 0. 35 vs. 0. 47 ± O. 12 ,P 〈 O. 05 ） at first week, and tended to be higher at the 4th week and 8th week （P 〉0.05 ）. The mRNA expression of Dl14 and Hesl was similar between the two groups at the three time points. NICD1 protein level was increased at the first week in MI group as compared with control group （ 1.31 ± 0. 33 vs. O. 45±0. 11, P 〈 0. 05 ） , which tended also to be higher at the 4th week and 8th week post operation （P 〉0. 05）. For NF-κB activation study, the nuclear protein p65 content was higher at first week, 4th week and 8th week in MI group as compared with respective control groups （0.286±0.052 vs. 0.049±0.016 （P〈0.01）,0.247±0.056 vs. 0.043 ±0.018 （P〈0. O1）, 0.120± 0. 033 vs. 0. 044 ± 0. 009 （P 〈 0. 05 ））, the most significant increase was found in the first week. Conelusions Notch and NF-KB signaling pathways are actively involved in the process of ventricular remodeling after myocardial infarction. Notchl and NF-KB signaling pathways are both activated at the first week after myocardial infarction, NF-KB signaling pathway activation after myocardial infarction continues up to 8 weeks. T

关 键 词：心肌梗死 NF-ΚB 心室重构 

分 类 号：R542.22[医药卫生—心血管疾病]