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|本期目录/Table of Contents|

阻断CXCR3通路在心肌缺血/再灌注损伤中的保护作用及机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第1期
页码:
11-015
栏目:
基础研究
出版日期:
2014-09-25

文章信息/Info

Title:
Protective and immunomodulatory effects of CXCR3 against cardiac ischemia-reperfusion injury
作者:
张 昕; 李 伟; 伍 勇; 徐 慧; 袁晓晨
(扬州市第一人民医院心血管内科，江苏 扬州 225001)
Author(s):
ZHANG Xin;  LI Wei;  WU Yong;  XU Hui;  YUAN Xiao-chen
(The Department of Cardiology, First Hospital of Yangzhou, Yangzhou 225001, Jiangsu, China)
关键词:
趋化因子受体; 心肌缺血/再灌注损伤; 拮抗剂
Keywords:
CXCR3;  mycardial ischemia-reperfusion injury;  antagonist
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的:研究趋化因子受体(CXCR)3在心肌缺血/再灌注损伤(IRI)中的作用及机制。方法： 建立大鼠IRI模型，分别获取假手术组，缺血/再灌注(I/R)后2 h、6 h、9 h和12 h组各时间点的心肌组织，分别利用实时定量PCR、Western blot分别检测趋化因子(CXCL)9-11及其受体CXCR3的mRNA及蛋白表达。利用CXCR3的特异性阻断剂6C干预I/R后6 h和9 h，通过HE染色分析心脏组织形态，利用基质速率法检测肌酸激酶同工酶MB（CK-MB）和乳酸脱氢酶(LDH)活性评价心肌损伤的程度。通过流式细胞仪检测浸润的炎症细胞亚群的分布等。结果： 与假手术组相比较，趋化因子CXCL9-11及其受体CXCR3在I/R后各时间点的表达显著增高（P<0.01），阻断CXCR3能够显著保护心肌的功能及心肌的形态，以及在有效降低Th1细胞的同时增加调节性T细胞(Treg)的浸润。结论： CXCR3是一个理想的可用于治疗IRI的靶点，其作用机制与免疫调节有关。
Abstract:
AIM:To investigate the role of CXCR3 in cardiac ischemia-reperfusion injury (IRI). METHODS: IRI rat model was set up and fresh myocardium tissues were obtained from sham and 2, 6, 9, and 12 h models after IRI. Expressions of CXCL9-11 and their receptor, CXCR3, were detected by real-time and Western blot. The effect of CXCR3 was blocked by its specific antagonist 6C. Myocardial injury was estimated by activity of cardiac-related enzyme activity and morphological indices. The distribution of subset of infiltrated T cells was analyzed by flow cytometry. RESULTS: Significant upregulation of both CXCL9-11 and CXCR3 was detected in varied time frames after reperfusion. Blockage of CXCR3 exerted structural and functional protective effects that were verified and were due to immunomodulation of myocardial tissues by CXCR3 of downregulation of Th1 and upregulation of T-regs. CONCLUSION: CXCR3 is an ideal therapeutic target in cardiac IRI due to its immunomodulatory effect.

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备注/Memo

备注/Memo:
收稿日期：2013-11-15.
通讯作者：袁晓晨，主任医师，主要从事冠心病基础和临床研究Email：13665288033@163.com
作者简介：张昕，副主任医师Email：zhangswy@126.com
更新日期/Last Update: 2015-01-20