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Title:: Protective effects of Notch signaling pathway on hypoxia/reoxygenation cardiac myocytes

作者:: 陈希瑶¹; 万卓²; 赵桐²; 郭海涛¹; 樊荣¹; 贾敏¹; 裴建明¹; (第四军医大学：1.基础部生理学教研室，2.学员旅15队，陕西西安 710032)

Author(s):: CHEN Xi-yao¹; WAN Zhuo²; ZHAO Tong²; GUO Hai-tao¹; FAN Rong¹; JIA Min¹; PEI Jian-ming¹; (1.Department of Physiology, 2.Team 13, Cadet Brigade, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)

关键词:: Notch; 信号途径; 缺氧/复氧; 心肌细胞; 乳鼠

Keywords:: Notch; reactive oxygen species; hypoxia/reoxygenation; apoptosis

分类号:: Q28；R542.2

DOI:: -

文献标识码:: A

摘要:: 目的:观察缺氧/复氧(H/R)后Notch信号途径相关分子的变化及阻断Notch信号途径对在H/R条件下乳鼠心肌细胞凋亡的影响。方法：将乳鼠心肌细胞分为常氧组和H/R组，每组再分为3组，即对照组、二甲基亚砜(DMSO)组及抑制Notch信号途径的γ分泌酶抑制剂(GSI)组。分别用实时PCR和Western blot检测Notch信号途径相关分子mRNA及其蛋白表达的水平。用原位缺口末端标记法(TUNEL)染色观察心肌细胞凋亡。用荧光探针DCFH-DA检测心肌细胞内活性氧簇(ROS)水平的变化。结果： H/R后，Notch信号途径相关分子的mRNA及其蛋白的水平、ROS水平及心肌细胞的凋亡与DMSO组相比均显著增加(P<0.01)。加入GSI后，对Notch信号途径上游的配基及受体的水平没有显著的影响，但对其下游的转录因子Hes1却可以显著抑制其表达，此时ROS的水平和心肌细胞凋亡进一步增加。结论： Notch信号途径在H/R后反应性上调可能对心肌细胞具有保护作用，该作用可能与抑制ROS的水平有关。

Abstract:: AIM:To observe the changes of Notch signaling pathway related molecules after hypoxia/reoxygenation and the effect of Notch signaling pathway blockage on apoptosis induced by myocardial hypoxia/reoxygenation. METHODS: Cardiac myocytes were divided into normoxic group and hypoxia/reoxygenation group and each group was further divided into three groups: control group, DMSO group and GSI (gamma secretase inhibitors) group. Notch signaling molecule mRNA and protein expression level were detected by real-time PCR and Western blot. Apoptotic cells were observed by TUNEL staining and intracellular ROS levels were assayed using fluorescence probe DCFH-DA. RESULTS: mRNA and protein level of Notch signaling pathway related molecules and apoptosis and ROS levels increased significantly after hypoxia/reoxygenation. The administration of GSI produced no significant effects on ligand and receptor of the upstream of Notch signaling pathway but significantly inhibited the expression level of Hes1, a downstream transcription factor of Notch signaling pathway. At the same time, ROS and apoptosis further increased. CONCLUSION: Upregulation of the Notch signaling pathway after hypoxia/reoxygenation may exert protective effects on cardaic myocytes, which is probably related to the decreased level of ROS.

参考文献/References

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Notch信号途径对缺氧/复氧乳鼠心肌细胞的保护作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

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