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作 者:理国富[1] 刘子由[1] 陈光献[1] 杜尚明[1] 梁孟亚[1] 姚尖平[1] 吴钟凯[1]
机构地区:[1]中山大学附属第一医院心脏外科,广州510080
出 处:《中华实验外科杂志》2015年第4期808-810,共3页Chinese Journal of Experimental Surgery
基 金:国家自然科学基金资助项目(30525020);国家自然科学青年基金资助项目(81000061);广东国际合作基金资助项目(20078050200024)
摘 要:目的 观察N-甲基-D-天冬氨酸受体1(NMDAR1)及谷氨酸转运体(EAAT2)在心肌肥厚大鼠心脏中的表达.方法 采用腹主动脉结扎制备心肌肥厚模型,64只F344雄性大鼠随机分为结扎后2、3、4和8周组,每组组内再进一步分为实验组和对照组(n=8).采用超声心动图证实心肌肥大模型的建立,并采用免疫荧光法检测连接蛋白43(Cx43)、NMDAR1和EAAT2的表达.结果 通过测定室间隔舒张末期厚度(IVSTd)和左室后壁舒张末期厚度(PWLVd),证实心肌肥厚模型建立成功.腹主动脉结扎术后3周,心肌肥厚达到最大[(1.72±0.17) mm比(1.29±0.24) mm、(2.12±0.12) mm比(1.43±0.37) mm,P< 0.05].在腹主动脉结扎术后3周及4周,心肌NMDAR1及EAAT2的阳性表达面积(Area,%)和积分吸光度(IA,%)显著升高(术后4周,NMDAR1:1.51±0.45比0.79±0.63、1.11±0.29比0.60 ±0.17,EAAT2:1.69±0.47比0.99±0.53,1.31±0.39比0.90±0.47,P<0.05);术后3、4及8周,心肌Cx43 Area(%)和IA(%)也明显升高(术后4周:2.51±0.85比1.11 ±0.33、1.94±0.66比0.80±0.55,P<0.05).结论 心肌肥厚大鼠心肌细胞中NMDAR1和EAAT2的表达明显上调,证实谷氨酸信号系统参与了心肌肥厚的重构过程.在心肌肥厚重构后第8周,NMDAR1和EAAT2的效应降低,而Cx43的效应则相对持续较长时间.Objective To investigate the expression of N methyl D asparate receptor 1 (NMDAR1) and excitatory amino acid transporters 2 (EAAT2) in hypertrophic cardiomyocytes in rats.Methods Using abdominal aortic-occluded myocardial hypertrophy model,64 male F344 rats were randomly assigned into post-occlusion 2 weeks,3 weeks,4 weeks and 8 weeks groups.Each group was further divided as the study subgroup or control subgroup.Myocardial hypertrophy was comfirmed by echocardiography,and connexin43 (Cx43),NMDAR1 and EAAT2 expression was detected by immunofluorescence.Results Myocardial hypertrophy was confirmed with the examinations of IVSTd and PWLVd.The most thickness hypertrophy heart was found at 3rd week after aortic-occlusion [(1.72 ± 0.17)mm vs.(1.29 ± 0.24) mm,and (2.12 ± 0.12) mm vs.(1.43 ± 0.37) mm,P 〈 0.05 for all].Area,% and IA,% of the expression of myocardial NMDAR1 and EAAT2 were significantly higher in hypertrophy myocardium at 3rd and 4th week after aortic-occlusion (at 4th week after aortic-occlusion,for NMDAR1:1.51±0.45 vs.0.79 ±0.63 and 1.11 ±0.29 vs.0.60 ±0.17,and for EAAT2:1.69 ±0.47 vs.0.99 ±0.53 and 1.31 ±0.39 vs.0.90 ±0.47,P 〈0.05 for all).Area,% and IA% of the expression of Cx43 in myocardium were significantly higher in hypertrophy myocardium at 3rd,4th and 8th week after aortic-occlusion (at 4th week after aortic-occlusion,2.51 ± 0.85 vs.1.11 ± 0.33,and 1.94 ±0.66 vs.0.80 ± 0.55,P 〈 0.05).Conclusion The up-regulation of NMDAR1 and EAAT2 in hypertrophic cardiomyocytes suggested that glutamate signal system participated in the myocardial hypertrophy remodeling process.The effects of NMDAR1 and EAAT2 decreased at 8th week after hypertrophy remodeling,and those of Cx43 resustained for relatively longer time.
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