STAT3在sRAGE抑制缺血再灌注导致的心肌细胞凋亡中的作用

doi:10.3969/j.issn.1006-7795.2016.01.009

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (1): 41-47.doi: 10.3969/j.issn.1006-7795.2016.01.009

• 心脑血管疾病临床与基础研究 • 上一篇下一篇

STAT3在sRAGE抑制缺血再灌注导致的心肌细胞凋亡中的作用

郭彩霞¹, 江雪¹, 曾翔俊², 陈步星¹

1. 首都医科大学附属北京天坛医院心内科, 北京 100050;
2. 首都医科大学基础医学院病理生理学教研室, 北京 100069

收稿日期:2015-12-10 出版日期:2016-02-21 发布日期:2016-02-01
通讯作者: 陈步星 E-mail:chbux@126.com
基金资助:
首都特色临床应用研究(Z131107002213106),北京市卫生系统高层次卫生技术人才培养计划(2011-3-026)。

Effect of STAT3 in soluble receptor for advanced glycation end-products inhibiting myocardial apoptosis induced by ischemia/reperfusion

Guo Caixia¹, Jiang Xue¹, Zeng Xiangjun², Chen Buxing¹

1. Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
2. Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Received:2015-12-10 Online:2016-02-21 Published:2016-02-01
Supported by:
This study was supported by Capital Special Study of Clinical Application(Z13117002213106), Beijing Health System High Level Health Technical Personnel Training Plan(2011-3-026).

摘要/Abstract

摘要： 目的建立体内和体外缺血再灌注(ischemia/reperfusion, I/R)模型,观察缺血再灌注心肌细胞凋亡情况及STAT3蛋白表达变化;检测sRAGE对缺血再灌注心肌细胞凋亡及STAT3的蛋白表达的影响。方法复制C57BL/6J小鼠心脏和原代心肌细胞缺血再灌注模型,在sRAGE和(或)STAT3抑制剂AG490的干预下,通过检测TUNEL及caspase-3活性评价心肌细胞凋亡的程度;通过Western blotting检测磷酸化的STAT3(p-STAT3)及总的STAT3(t-STAT3)蛋白的表达。结果体内实验,与Sham组相比,I/R组TUNEL阳性细胞数目和caspase-3活性分别增加了115%和120%,I/R组p-STAT3/STAT3比值降低了50%,sRAGE降低了I/R诱导的心肌细胞凋亡,包括TUNEL阳性细胞数目降低了51%,caspase-3活性降低了36%,此外,sRAGE预处理I/R组的p-STAT3/STAT3比值增加了381%; 体外实验,与Control组相比,I/R组TUNEL阳性细胞数目和caspase-3活性分别增加了380%和77%,I/R组p-STAT3/STAT3比值降低了69%,sRAGE(900 ng/mL)同样降低了I/R诱导的心肌细胞凋亡,表现为TUNEL阳性细胞数目降低了63%,caspase-3活性降低了33%,此外,sRAGE预处理I/R组的p-STAT3/STAT3比值增加了243%,与I/R+sRAGE组相比较,I/R+sRAGE+AG490组的TUNEL阳性细胞数目升高了126%,caspase-3活性增加了42%,p-STAT3/STAT3比值降低了68%。结论 sRAGE可通过激活STAT3抑制缺血再灌注诱导的心肌细胞凋亡。

关键词: sRAGE, 心肌缺血再灌注, 凋亡, STAT3

Abstract: Objective To test the effect of sRAGE on myocardial apoptosis and STAT3 protein expression with or without STAT3 inhibitor AG490 following ischemia/reperfusion in vivo and in vitro. Methods C57BL/6J mice undergone left anterior descending coronary artery ligation were used as in vivo model and neonatal rat cardiomyocyte subjected to ischemic buffer as an in vitro model. Apoptosis was detected by TUNEL staining and caspase-3 activity. Expression of STAT3/p-STAT3 protein were detected by Western blotting analysis in the presence and absence of the JAK2 inhibitor AG 490. Results In vivo, compared with sham group, the number of TUNEL positive cells and caspase-3 activity were increased by 115% and 120%, and the ratio of p-STAT3/STAT3 was reduced by 50%; sRAGE (100 μg/day) reduced the TUNEL-positive myocytes by 51%, and activity of caspase-3 by 36%, increased the ratio of p-STAT3/STAT3 by 381% followed by I/R. In vitro, compared with control group, the number of TUNEL positive cells and caspase-3 activity increased by 380% and 77%, and the ratio of p-STAT3/STAT3 was reduced by 69%, sRAGE (900 ng/mL) reduced the TUNEL-positive myocytes by 63%, and caspase-3 activity by 33%, increased the ratio of p-STAT3/STAT3 by 243% followed by I/R. The effect of sRAGE reduction on TUNEL-positive myocytes and caspase-3 activity, raise of the ratio of p-STAT3/STAT3 were attenuated by STAT3 inhibitor AG490. Conclusion These results suggest that sRAGE protects cardiomyocytes from apoptosis induced by I/R in vitro and in vivo by activating STAT3.

Key words: sRAGE, myocardial ischemia/reperfusion, apoptosis, STAT3

中图分类号:

R541.4

郭彩霞, 江雪, 曾翔俊, 陈步星. STAT3在sRAGE抑制缺血再灌注导致的心肌细胞凋亡中的作用[J]. 首都医科大学学报, 2016, 37(1): 41-47.

Guo Caixia, Jiang Xue, Zeng Xiangjun, Chen Buxing. Effect of STAT3 in soluble receptor for advanced glycation end-products inhibiting myocardial apoptosis induced by ischemia/reperfusion[J]. Journal of Capital Medical University, 2016, 37(1): 41-47.

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STAT3在sRAGE抑制缺血再灌注导致的心肌细胞凋亡中的作用

Effect of STAT3 in soluble receptor for advanced glycation end-products inhibiting myocardial apoptosis induced by ischemia/reperfusion

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