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抑制GSK-3β减轻大鼠急性心肌缺血/再灌注损伤的作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第5期
页码:
589-593
栏目:
基础研究
出版日期:
2011-10-25

文章信息/Info

Title:
Glycogen synthase kinase-3β inhibition protects heart from acute ischemia/reperfusion injury
作者:
殷 忠1; 薛 白2; 高好考3; 王海昌3; 杨 晔1
海军总医院：1.心内科，2.消化科，北京 100048；3.第四军医大学西京医院心内科，陕西 西安 710032
Author(s):
YIN Zhong1;  XUE Bai2;  GAO Hao-kao3;  WANG Hai-chang3;  YANG Ye1
1.Department of Cardiology, 2.Department of Gastroenterology, Navy General Hospital, Beijing 100048, China; 3.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
糖原合酶激酶-3β; 缺血/再灌注损伤; 炎症; 核因子-κB ; 大鼠
Keywords:
glycogen synthase kinase-3β;  ischemia/reperfusion injury;  inflammation;  nuclear factor- kappa B
分类号:
R542.22
DOI:
-
文献标识码:
A
摘要:
目的:评估糖原合酶激酶-3β（GSK-3β）抑制剂TDZD-8减轻大鼠急性心肌缺血/再灌注损伤(MIRI)的作用，并探讨此作用是否与其下调NF-κB、抑制炎症有关。方法： 取健康雄性SD大鼠60只，随机分为缺血/再灌注(I/R)组、I/R+TDZD组、I/R+载体(Vehicle,V)组及假手术（Sham）组。大鼠局部心肌缺血30 min，再灌注3 h。用TTC染色计算心肌梗死面积，HE染色及ELISA法评估心肌组织中中性粒细胞浸润及炎性因子(TNF-α和IL-6)的变化；用Western blot测定心肌组织中NF-κB、GSK-3β磷酸化的水平。结果： TDZD-8能明显降低心肌梗死的面积和心肌组织中性粒细胞浸润、抑制NF-κB激活以及心肌源性TNF-α和IL-6的浓度(P<0.01)。结论： GSK-3β抑制剂TDZD-8能够减轻MIRI，其作用可能与其抑制NF-κB的激活及炎症反应有关。
Abstract:
AIM:To investigate the effects of TDZD-8, a GSK-3β inhibitor, on acute myocardial ischemia/reperfusion injury and to determine whether the protection is associated with the downregulation of NF-κB and the inhibition of inflammation. METHODS: Sixty healthy male Sprague Dawley rats were randomly divided into ischemia/reperfusion (I/R group), ischemia/reperfusion+drug group (I/R+D group), ischemia/reperfusion+vehicle group (I/R+V group) and sham group. Rats were subjected to 30 min ischemia followed by 3 h reperfusion. Myocardial infarct sizes were detected by TTC staining and myocardial tissue neutrophil infiltration. Changes in inflammatory factors were evaluated using HE staining and ELISA method. Phosphorylation of NF-κB and GSK-3β was measured by Western blotting. RESULTS: TDZD-8 reduced the infarct size and neutrophil infiltration (P<0.01) and inhibited NF-κB activation (P<0.01) and levels of cardiac-derived TNF-α and IL-6 (P<0.01). CONCLUSION: GSK-3β inhibitor, TDZD-8, can protect myocardial ischemia/reperfusion injury and may be related to the inhibition of NF-κB activation and the inhibition of inflammation.

参考文献/References

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[3]Cuzzocrea S,Mazzon E,Esposito E,et al.Glycogen synthase kinase-3beta inhibition attenuates the development of ischaemia/reperfusion injury of the gut[J].Intensive Care Med,2007,33(5):880-893.

[4]Collino M,Thiemermann C,Mastrocola R,et al.Treatment with the glycogen synthase kinase-3beta inhibitor,TDZD-8,affects transient cerebral ischemia/reperfusion injury in the rat hippocampus[J].Shock,2008,30(3):299-307.

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备注/Memo

备注/Memo:
收稿日期：2010-11-25.通讯作者：王海昌，主任医师，主要从事冠心病的诊断与治疗研究Email:wanghc@fmmu.edu.cn 共同通讯作者：杨晔，主任医师，主要从事冠心病、OSAS与心血管病关系研究Email:yangye0407@sina.com 作者简介: 殷忠，主治医师，博士Email:ouandyin1219@163.com
更新日期/Last Update: 2011-11-03