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大麻素Ⅱ型受体激动剂促进小鼠心肌梗死后心脏干/祖细胞增殖的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第3期
页码:
265-270
栏目:
基础研究
出版日期:
2014-03-20

文章信息/Info

Title:
CB2 receptor agonist promotes cardiac stem/progenitor cell proliferation in a mouse model of myocardial infarction
作者:
胡文星; 王亚斌; 刘 通; 李秀娟; 马 赛; 梁 栋; 曹 丰
(第四军医大学西京医院心内科，陕西 西安 710032)
Author(s):
HU Wen xing;  WANG Ya bin;  LIU Tong;  LI Xiu juan;  MA Sai;  LIANG Dong;  CAO Feng
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
大麻素Ⅱ型受体; 心肌梗死; 心脏干/祖细胞; 大鼠
Keywords:
cannabine receptor II;  myocardial infarction;  cardiac stem/progenitor cell;  rat
分类号:
R282.71
DOI:
-
文献标识码:
A
摘要:
目的:探讨大麻素Ⅱ型受体（CB2）选择性激动剂AM1241对小鼠心肌梗死(MI)模型中心脏干/祖细胞增殖的作用。方法:40只雄性C57BL/6小鼠通过结扎小鼠心脏左冠状动脉前降支建立MI模型并随机分为4组，每组10只(n=10)：①假手术（Sham）组；②MI组；③MI+CB2受体激动剂AM1241（MI+AM1241）组；④MI+CB2受体激动剂AM1241+CB2受体拮抗剂AM630（MI+AM1241+AM630）组。采用小动物超声系统观察小鼠左室射血分数（LVEF）的变化。用免疫荧光染色法观察MI周边区表达干细胞生长因子受体（c-kit）、干细胞抗原1（Sca-1）的阳性细胞数，实时荧光定量PCR测定MI周边区c-kit、Sca-1和多药耐药蛋白P糖蛋白（MDR1）的表达水平。结果:与MI组相比，MI+AM1241组小鼠7 d和14 d心脏LVEF值显著提高（P<0.01）。免疫荧光染色的结果提示，MI+AM1241组c-kit和Sca-1的表达较MI组增多（P<0.05）。实时荧光定量PCR结果显示，MI+AM1241组c-kit和Sca-1的基因表达水平明显高于MI组（P<0.05）。同时，CB2受体拮抗剂AM630可阻断AM1241的上述作用。结论:CB2受体激活可促进梗死心肌干/祖细胞的增殖，改善心脏的收缩功能。
Abstract:
AIM:To observe the effect of cannabinoid receptor II (CB2) activation on cardiac stem/progenitor cell proliferation in mice myocardial infarction (MI) models. METHODS: C57BL/6 male mice were randomly allocated into four groups: Sham group (Sham), MI group (MI), MI+CB2 agonist AM1241 group (MI+AM1241), and MI+CB2 agonist AM1241+CB2 antagonist AM630 group (MI+AM1241+AM630). Mice MI model was induced by ligation of the left anterior descending artery. Echocardiography was performed to evaluate left ventricular ejection fraction (LVEF). The number of cardiac stem/progenitor cells was observed with immunostaining for cardiac stem/progenitor cell surface markers c-kit and Sca-1 in peri-infarction region at day 7 post MI. Real-time PCR analysis was conducted to examine the expression of c-kit, Sca-1 and MDR1 in the border zone of infarcted myocardium at day 7 and 14 post-MI. RESULTS: Echocardiography revealed that AM1241 ameliorated LVEF compared with that in MI group at day 7 (P<0.01) and day 14 (P<0.01) post-MI. Both immunofluorescence staining and RT-PCR demonstrated that the administration of AM1241 significantly increased the expression of c-kit and Sca-1 in the border zone of infarcted myocardium (P<0.05) and the protective effect of AM1241 on the infarcted myocardium was inhibited by CB2 antagonist AM630. CONCLUSION: CB2 receptor activation may promote cardiac stem/progenitor cell proliferation and improve cardiac systolic function.

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备注/Memo

备注/Memo:
收稿日期：2013-11-02.
基金项目：国家自然科学基金项目资助(81270168)；军队十二五重点项目资助(FCao BWS12J037)；教育部创新团队发展基金项目资助(2010CXTD01，IRT1053)；国家重点基础研究发展规划项目资助(2012CB518101)。
通讯作者：曹丰，教授，主要从事心血管分子影像研究 Email：wind8828@gmail.com
作者简介：胡文星，硕士生 Email：jimmy860820@163.com
更新日期/Last Update: 2014-03-21