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中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (7): 766-769.

• 研究原著 • 上一篇    下一篇

一氧化氮诱导心肌细胞预适应早期保护作用的信号转导途径

张峰, 张涛1, 王志鹏, 王汝涛, 李晨, 梅其炳   

  1. 第四军医大学药理学教研室, 西安710033, 陕西;1第四军医大学唐都医院胸外科, 西安710038, 陕西
  • 收稿日期:2004-03-29 修回日期:2004-05-12 出版日期:2004-07-26 发布日期:2020-11-20
  • 通讯作者: 梅其炳,男,博士,教授,博士生导师,从事心血管分子药理和新药研究工作。Tel:029-83374552 E-mail:qbmei@fmmu.edu.cn
  • 作者简介:张峰,女,博士,讲师,从事心血管分子药理研究。Tel:029-83374555 E-mail:zf1218@yahoo.com.cn

Nitric oxide-induced early preconditioning of cardiac myocytes and its signal transduction pathways

ZHANG Feng, ZHANG Tao1, WANG Zhi-Peng, WANG Ru-Tao, LI Chen, MEI Qi-Bing   

  1. Department of Pharmacology, Fourth Military Medical University, Xian 710033, Shaanxi, China; 1Department of Thoracic Surgery, Fourth Military Medical University, Xian 710038, Shaanxi, China
  • Received:2004-03-29 Revised:2004-05-12 Online:2004-07-26 Published:2020-11-20

摘要: 目的: 探讨一氧化氮(NO)诱导心肌细胞预适应早期保护作用及可能的信号转导途径。方法: 体外培养新生大鼠心肌细胞,分别以NO合成前体L-精氨酸(L-Arg)和NO供体SNAP处理细胞,观察心肌细胞在随后6h的缺氧损伤程度,以明确NO是否诱导心肌细胞预适应早期保护作用;分别以cGMP阻断剂亚甲基蓝、蛋白激酶C(PKC)抑制剂D-鞘氨醇、钙拮抗剂拉西地平和ATP敏感的钾通道[K(ATP)通道]阻断剂格列苯脲作用心肌细胞30min后加入SNAP作用60min,观察心肌细胞缺氧损伤程度,检测指标为心肌细胞存活率及乳酸脱氢酶(LDH)活性。结果: SNAP和L-Arg均可诱导心肌细胞预适应早期保护作用,一氧化氮合酶抑制剂LNAME可阻断L-Arg的保护作用,亚甲基蓝可完全取消SNAP对缺氧心肌细胞的保护作用,D-鞘氨醇、拉西地平和格列苯脲均可减弱SNAP的作用。结论: NO可能通过cGMP依赖途径诱导心肌细胞预适应早期保护作用,而PKC 的活化和钙通道、K(ATP)通道的开放是其下游重要的环节。

关键词: 一氧化氮, 心肌细胞, 缺氧, 预适应, 信号转导

Abstract: AIM: To study nitric oxide-induced early preconditioning of cardiac myocytes and its signal transduction pathways.METHODS: Cultured neonatal rat cardiac myocytes were pretreated with SNAP and L-Arg respectively for 1 h.The injury of cardiac myocytes was detected after subsequent 6 h hypoxia to determine whether NO could induce early preconditioning.Cells were incubated with cGMP inhibitor methylene blue, protein kinase C (PKC) inhibitor D-sphingosine, calcium antagonist lacidipine and adenosine triphosphate sensitive potassium channel [ K (ATP) channel] blocker libenclamide respectively for half an hour.Cells were then treated with SNAP for 1 h.Cardiac myocytes injury was observed by detecting cell viability and lactate dehydrogenase (LDH).RESULTS: Both SNAP and L-Arg could induce early preconditioning of cardiac myocytes, nitric oxide synthase (NOS) inhibitor L-NAME block the protective effect of L-Arg, Methylene blue could completely abolish SNAPinduced cardioprotection, and D-sphingosine, lacidipine and glibenclamide weaken SNAP-induced protection.CONCLUSION: NO can induce early preconditioning protection of cardiac myocytes via cGMP-dependent pathway.Activation of PKC and opening of calcium channels and K(ATP) channels may be important downstream events of cGMP.

Key words: nitric oxide, cardiac myocyte, hypoxia, preconditioning, signal transduction

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