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| 激活Notch1通路减轻高温高湿条件下H9C2心肌细胞缺氧/复氧损伤 | |
| 引用本文： | 杨亚丽,胡建华,纪兆乐,尹志勇. 激活Notch1通路减轻高温高湿条件下H9C2心肌细胞缺氧/复氧损伤[J]. 心脏杂志, 2017, 29(5): 512-517 |
| 作者姓名： | 杨亚丽 胡建华 纪兆乐 尹志勇 |
| 作者单位： | （第四军医大学西京医院心血管内科，陕西 西安 710032） |
| 基金项目： | 全军后勤科研项目资助（CWS14J065）；国家自然科学基金项目资助（81570252；81500195） |
| 摘 要： | 目的明确Notch1通路在高温高湿条件下H9C2心肌细胞缺氧/复氧(Hypoxia/Reoxygenation,H/R)损伤中的作用及其潜在机制。方法常规培养H9C2心肌细胞并将其分6组即对照组;H/R组;高温高湿组;高温高湿+H/R组;高温高湿+Jagged1(Notch1激动剂)+H/R组;高温高湿+溶剂+H/R组。TUNEL法检测细胞凋亡,荧光探针JC-1检测线粒体膜电位,ATP检测试剂盒检测ATP含量,Western blot检测Notch1细胞内段(Notch1 intracellular domain,Notch1 ICD)、Hairy和分裂增强子(Hairy and enhancer of split,Hes1)、微管相关蛋白1轻链3(microtubuleassociated protein1 light chain 3,LC3)和p62的蛋白表达水平。结果与对照组相比,急性损伤H/R后,细胞凋亡增加(P0.05),线粒体膜电位降低(P0.05),ATP含量减少(P0.05),Notch1 ICD、Hes1、LC3-II/I(p62相应降低)表达升高(P0.05),而慢性损伤高温高湿后,细胞凋亡增加(P0.05),线粒体膜电位降低(P0.05),ATP含量减少(P0.05),Notch1 ICD、Hes1、LC3-II/I表达降低(p62相应升高)(P0.05);和H/R组或高温高湿组对比,高温高湿+H/R组中细胞凋亡进一步增加(P0.05),线粒体膜电位和ATP含量进一步降低(P0.05),Notch1ICD、Hes1、LC3-II/I表达进一步降低(p62进一步升高)(P0.05);和高温高湿+H/R组对比,加入Notch1激动剂Jagged1后,细胞凋亡减少(P0.05),线粒体膜电位和ATP含量增高(P0.05),Notch1 ICD、Hes1、LC3-II/I表达升高(p62相应降低)(P0.05)。结论激活Notch1通路通过促进自噬从而缓解高温高湿条件下H9C2心肌细胞缺氧/复氧损伤。 |
| 关 键 词： | ; ; ; |
| 收稿时间： | 2016-10-11 |
Activation of Notch1 pathway alleviates hypoxia/reoxygenation injury of H9C2 cardiomyocytes in high temperature and humidity |
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| Abstract: | AIM To investigate the role of Notch1 pathway and its underlying mechanisms in H9C2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury in high temperature and humidity. METHODS H9C2 cardiomyocytes were cultured and divided into six groups: control group, H/R group, high temperature and humidity group, high temperature and humidity+H/R group, high temperature and humidity+Jagged1 (an activator of Notch1)+H/R group and high temperature and humidity+vehicle+H/R group. Cell apoptosis was detected by TUNEL, mitochondrial membrane potential was assessed by JC-1 and ATP content was measured by an ATP bioluminescent assay kit. The expression of Notch1 intracellular domain (Notch1 ICD), Hairy and enhancer of split (Hes1), microtubule-associated protein1 light chain 3 (LC3) and p62 were analyzed by Western blot. RESULTS Compared with those in control group, H/R injury significantly increased cell apoptosis index (P<0.05), reduced mitochondrial membrane potential (P<0.05) and ATP content (P<0.05), and increased expressions of Notch1 ICD, Hes1 and LC3-II/I (except p62) (P<0.05). Although high temperature and humidity also increased cell apoptosis index (P<0.05), reduced mitochondrial membrane potential (P<0.05) and ATP content (P<0.05), it reduced expressions of Notch1 ICD, Hes1 and LC3-II/I (except p62) (P<0.05) compared with those in control group. In addition, compared with those in H/R group or high temperature and humidity group, cell apoptosis index further increased (P<0.05), mitochondrial membrane potential (P<0.05) and ATP content reduced (P<0.05), and the expressions of Notch1 ICD, Hes1 and LC3-II/I(except p62) decreased (P<0.05) in high temperature and humidity+H/R group. Moreover, compared with those in high temperature and humidity+H/R group, adding Jagged1 (an activator of Notch1) reduced cell apoptosis index (P<0.05) and increased the mitochondrial membrane potential (P<0.05) and ATP content (P<0.05) as well as the expressions of Notch1 ICD, Hes1 and LC3-II/I (except p62) (P<0.05). CONCLUSION Activation of Notch1 pathway can alleviate hypoxia/reoxygenation injury of H9C2 cardiomyocytes in high temperature and humidity through accelerating autophagy. |
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