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Title:: The mechanism of ET1 induced growthpromoting effect in cardiac myocytes

作者:: 朱肖星¹; 梅其炳¹; 刘莉¹; 吕顺艳²; 胡玉珍²; 张峰¹; 陈定章³; 裴兆辉²; 袁文俊⁴; 第四军医大学: 1.药理学教研室, 2.生理学教研室, 3.西京医院超声科,陕西西安 710032; 4.第二军医大学生理学教研室，上海 200003

Author(s):: ZHU Xiaoxing¹; MEI Qibing¹; LIU Li1; LU Shunyan² ; HU Yuzhen²; ZHANG Feng¹; CHEN Dingzhang³; PEI Zhaohui² ; YUAN Wenjun⁴; 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 P

关键词:: 内皮素1; L型钙通道; 钙激活氯通道; 蛋白激酶C（PKC）途径; 细胞外信号调节的蛋白激酶(ERK)途径

Keywords:: endothelin1; Ltype calcium channel; calcium activated chlorine channel; protein kinase C; extracellular-signal regulated kinase

分类号:: R331.31

DOI:: -

文献标识码:: A

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(larcidipine)和MN9202、钙激活氯通道阻断剂尼氟灭酸(niflumic acid,NFA）、蛋白激酶C(protein kinase 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±20 μg/ml，ET1组为312±30 μg/ml，较对照组升高14%。ET1+NFA组、ET1+che组、ET1+MN9202组、ET1+larcidipine组、ET1+PD98059组分别为280±10 μg/ml、283±10 μg/ml、285±27 μg/ml、275±22 μg/ml、293±33 μg/ml；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。

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.

参考文献/References

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内皮素1对新生大鼠心肌细胞的影响及机制(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

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