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FoxO1变化对糖尿病小鼠心肌缺血/再灌注损伤的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第3期
页码:
303-307
栏目:
基础研究
出版日期:
2012-06-25

文章信息/Info

Title:
Effect of myocardial FoxO1 variation on cardiac ischemia/reperfusion injury in diabetic mice
作者:
冯世栋; 孙 璐; 路晓艳; 杨 强; 刘静祎; 王海昌; 陶 凌
(第四军医大学西京医院心血管内科，陕西 西安 710032)
Author(s):
FENG Shi-dong;  SUN Lu;  LU Xiao-yan;  YANG Qiang;  LIU Jing-yi;  WANG Hai-chang;  TAO Ling
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
插头转录因子O1; 糖尿病; 缺血/再灌注损伤; 心肌
Keywords:
FoxO1;  diabetes;  ischemia/reperfusion injury;  myocardium
分类号:
R587.1
DOI:
-
文献标识码:
A
摘要:
目的:观察心肌中插头转录因子O1（FoxO1）在糖尿病（DM）小鼠心肌中表达量变化及对小鼠心肌缺血/再灌注（I/R）损伤的影响。方法： 将90只健康雄性Swiss小鼠随机分为5组：假手术（Sham）组、I/R组、DM+Sham组、DM+I/R组及DM+FoxO1SiRNA+I/R组，每组18只。采用高糖高脂饮食加链脲菌素(Streptozocin，STZ)腹腔注射诱导建立DM小鼠模型。采用FoxO1SiRNA心肌点注射下调心肌FoxO1表达。心肌I/R损伤模型的建立，采用结扎心脏冠状动脉左前降支30 min后再灌注方案实施。心肌再灌注3 h后，用原位缺口末端标法(TUNEL)检测心肌细胞凋亡。用ELISA法检测心肌中 Caspase-3的活性。用Western blot法检测心肌中FoxO1的表达量。心肌再灌注24 h后，用2,3,5-三苯基氯化四氮唑（TTC）染色法检测心肌梗死（MI）的面积。结果： 与Sham组比较，DM+Sham组心肌中FoxO1的表达量明显增高（P<0.01）。与I/R组比，DM+I/R组MI的面积增大（P<0.05），心肌细胞凋亡数量及Caspase-3活性明显增加（P<0.01）。与DM+I/R组相比，DM+FoxO1SiRNA+I/R组心肌FoxO1的表达量下调（P<0.05），MI面积及Caspase-3的活性减小（P<0.05），心肌细胞凋亡数量减少（P<0.01）。结论： DM小鼠心肌中FoxO1表达量的增加可加重心肌I/R损伤；而下调心肌中FoxO1的表达量后，心肌I/R损伤减轻。
Abstract:
AIM:To investigate the effect of myocardial FoxO1 expression on myocardial ischemia/reperfusion injury in diabetic mice. METHODS: Ninety male Swiss mice were randomly divided into five groups: control group, I/R group, DM+control group, DM+I/R group, and DM+FoxO1SiRNA+I/R group. Diabetic mice model was induced by low-dose i.p. STZ injection along with a diet high in sugar and fat. The FoxO1SiRNA interference was implemented by injection into the apex and anterolateral wall of the heart. Myocardial ischemia injury was produced by slip-knot ligature of the left anterior descending coronary artery for 30 min, and the myocardium was reperfused for 3 h (for FoxO1 expression by Western blot, caspase-3 by ELISA and apoptosis by TUNEL) or 24 h (for infarct size by TTC staining). RESULTS: Compared with the control group, FoxO1 expression of myocardium increased in DM+control group (P<0.01). Compared with I/R group, the infarct area size (P<0.05), myocardial apoptosis and caspase-3 activity (P<0.01) increased in DM+I/R group. After decreasing myocardial FoxO1 expression in DM+FoxO1SiRNA+I/R mice (P<0.05), caspase-3 activity (P<0.01), infarct area size and myocardial apoptosis (P<0.05) decreased in DM+FoxO1SiRNA+I/R group compared with DM+I/R group. CONCLUSION: High expression of myocardial FoxO1 increases cardiac vulnerability to myocardial I/R injury in diabetic mice. Downregulation of myocardial FoxO1 expression attenuates myocardial I/R injury.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2011-10-24.基金项目：国家自然科学基金项目资助（81100136） 通讯作者：陶凌，教授，主要从事糖尿病心肌损伤研究 Email：Lingtao2006@gmail.com 共同通讯作者：王海昌，主任医师，主要从事冠心病研究 Email:wanghc@fmmu.edu.cn 作者简介：冯世栋，硕士生 Email:fengshidong2009@163.com
更新日期/Last Update: 2012-05-02