| 引用本文: | 李文畅,马晓倩,李玉璟,张丽志,李蒙蒙,方瑞,温克.1-磷酸鞘氨醇对心肌缺血再灌注损伤所致细胞凋亡的影响及其与PI3K/Akt/GSK3β通路的相关性研究[J].中国现代应用药学,2017,34(2):151-155. |
| LI Wenchang,MA Xiaoqian,LI Yujing,ZHANG Lizhi,LI Mengmeng,FANG Rui,WEN Ke.Effects of Sphingosine-1-phosphate on Apoptosis Induced by Myocardial Ischemia-reperfusion Injury and Its Correction with PI3K/Akt/GSK3β Pathway[J].Chin J Mod Appl Pharm(中国现代应用药学),2017,34(2):151-155. |
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| 摘要: |
| 目的 研究1-磷酸鞘氨醇（sphingosine 1-phosphate，S1P）对心肌缺血再灌注损伤（myocardial ischemia/reperfusioninjury，MIRI）所致细胞凋亡的影响及其与PI3K/Akt/GSK3β信号通路的相关性。方法 缺血30 min后，进行再灌注损伤120 min，建立大鼠MIRI模型。采用TTC染色方法测定心肌梗死面积，采用TUNEL染色方法观察心肌凋亡指数，采用酶联免疫方法测定血浆CK-MB活性。采用Western blot方法测定Akt、GSK3β磷酸化情况以及cleaved caspase-3水平，并测定细胞色素C释放情况。结果 S1P可明显减少心肌梗死面积、降低细胞凋亡指数。同时增加Akt、GSK3β磷酸化程度，降低cleaved caspase-3水平，减少胞浆细胞色素C易位。S1P的保护作用可被PI3K抑制剂LY294002所阻断。结论 S1P可通过抑制线粒体蛋白细胞色素C释放、减少caspase激活，减弱MIRI所致心肌细胞凋亡以及心肌梗死，该作用与PI3K/Akt/GSK3β信号通路活化有关。 |
| 关键词: 1-磷酸鞘氨醇 缺血再灌注损伤 凋亡 PI3K/Akt |
| DOI：10.13748/j.cnki.issn1007-7693.2017.02.001 |
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| 基金项目:国家自然科学基金项目（81173058，81502419），天津市大学生创新创业训练计划项目（201610062021） |
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| Effects of Sphingosine-1-phosphate on Apoptosis Induced by Myocardial Ischemia-reperfusion Injury and Its Correction with PI3K/Akt/GSK3β Pathway |
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LI Wenchang1, MA Xiaoqian1, LI Yujing1, ZHANG Lizhi2, LI Mengmeng1, FANG Rui1, WEN Ke1
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1.Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;2.Department of Obstertrics and Gynecology, Tianjin First Center Hospital, Tianjin 300192, China
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| Abstract: |
| OBJECTIVE To investigate the effect of sphingosine 1-phosphate (S1P) on cell apoptosis induced by myocardial ischemia/reperfusion injury(MIRI), and its correlation with PI3K/Akt/GSK3β pathway.METHODS Rats were subjected to MIRI, consisting of 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size and apoptotic index were measured by triphenyltetrazolium (TTC) and terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL) assays, respectively. Plasma CK-MB activity was measured by enzyme linked immunosorbent assay. Akt and GSK3β phosphorylation, caspase-3 cleavage, and cytochrome C translocation were assessed by western blot.RESULTS S1P significantly decreased myocardial infarct size and apoptosis, as well as enhanced Akt and GSK3β phosphorylation, attenuated caspase-3 cleavage and cytosolic cytochrome C translocation. Moreover, the protective effects of S1P treatment were blocked by cotreatment with a PI3K inhibitor, LY294002.CONCLUSION S1P can inhibit the release of mitochondrial cytochrome C, block activation of caspase-3, relieve cellular apoptosis and myocardial infarction. And these effects are mediated by activation of PI3K/Akt/GSK3β pathway. |
| Key words: sphingosine 1-phosphate myocardial ischemia/reperfusion injury apoptosis PI3K/Akt |
