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  

CB_2 receptor agonist promotes cardiac stem/progenitor cell proliferation in a mouse model of myocardial infarction

作　　者：胡文星[1] 王亚斌[1] 刘通[1] 李秀娟[1] 马赛[1] 梁栋[1] 曹丰[1] 

机构地区：[1]第四军医大学西京医院心内科,陕西西安710032

出　　处：《心脏杂志》2014年第3期265-270,共6页Chinese Heart Journal

基　　金：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)

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。AIM： To observe the effect of cannabinoid receptor Ⅱ（ CB2 ） activation on cardiac stem/pro genitor 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. Echo cardiography was performed to evaluate left ventricular ejection fraction （LVEF）. The number of cardiac stem/progenitor ceils 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 stai ning and RT-PCR demonstrated that the administration of AM1241 significantly increased the expressionof 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 stern/progenitor cell proliferation and improve cardiac systolic function.

关 键 词：大麻素Ⅱ型受体 心肌梗死 心脏干 祖细胞 大鼠 

分 类 号：R282.71[医药卫生—中药学]