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

目的：探讨大麻素Ⅱ型受体（CB2）选择性激动剂AMl241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＋CB：受体激动剂AMl241（MI＋AMl241）组；④MI＋CB2受体激动剂AMl241＋CB2受体拮抗剂AM630（MI＋AMl241＋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（Sea-1）的阳性细胞数，实时荧光定量PCR测定MI周边区c-kit、Sea-1和多药耐药蛋白P糖蛋白（MDRl）的表达水平。结果：与MI组相比，MI＋AMl241组小鼠7d和14d心脏LVEF值显著提高（P〈0．01）。免疫荧光染色的结果提示，MI＋AMl241组c-kit和Sea-1的表达较MI组增多（P〈0．05）。实时荧光定量PCR结果显示，MI＋AMl241组c-kit和Sea-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AMl241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。

CB2 receptor agonist promotes cardiac stem/progenitor cell proliferation in a mouse model of myocardial infarction

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.