【作者】 朱肖星； 梅其炳； 刘莉； 吕顺艳； 胡玉珍； 张峰； 陈定章； 裴兆辉； 袁文俊；

【Author】 ZHU Xiao-xing~(1),MEI Qi-bing~(1),LIU Li~(1),LU Shun-yan~(2),HU Yu-zhen~(2),ZHANG Feng~(1),CHEN Ding-zhang~(3),PEI Zhao-hui~(2),YUAN Wen-jun~(4)(1.Department of Pharmacology,Faculty of Pharmacology;2.Department of Physiology,Faculty of(Preclinical) Medicine;3.Department of Ultrasound,Xijing Hospital,Fourth Military Medical University,(Xi′an),Shaanxi 710032;4.Department of Physiology,Faculty of Preclinical Medicine,Second Military Medical University,Shanghai 200003,China)

【机构】 第四军医大学药理学教研室； 第四军医大学生理学教研室； 第四军医大学西京医院超声科； 第二军医大学生理学教研室；

【摘要】 目的:研究内皮素-1(ET-1)诱导心肌肥大的机制及对抗的药物。方法:在培养新生大鼠心肌细胞中,采用L-型钙通道阻滞剂拉西地平(larc id ip ine)和MN9202、钙激活氯通道阻断剂尼氟灭酸(n iflum ic ac id,NFA)、蛋白激酶C(prote in k inase C,PKC)通路的阻断剂白屈菜季氨碱(chelerythrine,che)和ERK通路阻断剂PD98059(PD)观察内皮素-1在诱导心肌蛋白质合成中的影响。结果:对照组(DMEM)蛋白质含量为273±20μg/m l,ET-1组为312±30μg/m l,较对照组升高14%。ET-1+NFA组、ET-1+che组、ET-1+MN9202组、ET-1+larc id ip ine组、ET-1+PD98059组分别为280±10μg/m l、283±10μg/m l、285±27μg/m l、275±22μg/m l、293±33μg/m l;与ET-1组比较分别降低10%、9%、8.6%、13.1%、6.1%。结论:ET-1刺激引起的心肌细胞蛋白合成与钙激活氯通道和L-型钙通道有关,PKC和ERK通路在ET-1诱导心肌肥大的信号转导通路中起重要作用。更多还原

【Abstract】 AIM: To investigate the mechanism of cardiac myocyte hypertrophy induced by endothelin-1(ET-1).METHODS: ET-1 has been known to be a potent stimulator for neonatal rat ventricular myocyte(NRVM) hypertrophy in vitro.Chronic ET-1 stimulation produces increased cell size and protein synthesis.Over the past several years,cultured NRVM have been used to delineate the signaling pathways activated by ET-1.We studied the influence of protein synthesis stimulated by chronic ET-1 using the blockers of L-type calcium channel(larcidipine and MN9202),the inhibitor of calcium activated chlorine channel(niflumic acid,NFA),the inhibitor of protein kinase C(PKC)(chelerythrine,che) and the inhibitor of ERK(PD98059,PD).RESULTS: Intracellular protein contents in cardiac myocytes in each groups were: ET-1,312±30 μg/ml(14% higher than control,P<0.05);ET-1+NFA,280±10 μg/ml(10% lower than ET-1,P<0.05);ET-1+che,283±10 μg/ml(9% lower than ET-1,P<0.05);ET-1+MN9202,285±27 μg/ml(8.6% lower than ET-1,P>0.05);ET-1+Larcidipine,275±22 μg/ml(13.1% lower than ET-1,P<0.05);ET-1+PD98059,293±33 μg/ml(6.1% lower than ET-1,P>0.05).CONCLUSION: ET-1 induced growth-promoting in myocytes is associated with L-type calcium channels and calcium activated chlorine channels.PKC and ERK may be important intracellular signaling transduction pathways in ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes.更多还原