P-ERK、P-p38及iNOS、GLUT4在冠心病患者冬眠心肌中表达及意义

Significances of P-ERK,P-p38,iNOS and GLUT4 expressions in hibernating myocardium of patients with cardiac arterial disease

目的探讨冬眠心肌(HM)细胞内磷酸化ERK(P-ERK)、磷酸化p38(P-p38)、葡萄糖转运因子4(GLUT4)、诱导型一氧化氮合酶(iNOS)的变化和意义,探讨P-ERK、P-p38与GLUT4、iNOS的关系。方法选择行冠脉搭桥手术的冠心病患者10例,术前1周用多巴酚丁胺超声负荷试验结合多普勒组织成像确定HM及正常心肌(NM)的存在部位,术中根据检测结果取材,用免疫印迹法检测P-ERK、P-p38、iNOS、GLUT4的表达情况,分析HM与NM的P-ERK、P-p38、iNOS、GLUT4含量;分析四者之间的相关性。结果HM细胞内P-ERK、P-p38、GLUT4、iN-OS水平较正常心肌高;P-ERK与GLUT4呈正相关(r=0.665,P<0.05),P-p38与GLUT4、iNOS呈正相关(r=0.708、0.676,P<0.05)。结论心肌缺血缺氧可触发ERK、p38活化,活化的ERK、p38促使心肌细胞增加GLUT4及iNOS表达,促进HM形成。

Objective To observe changes of P-ERK, P-p38, inducible nitric oxide synthase （iNOS） and glucose transport type 4 （GLUT4） in hibernating myocardium（HM） and to explore the relationship of P-ERK, P-p38, iNOS and GLUT4. Methods Ten patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine stress echocardiography （DSE）, doppler tissue image （DTI） to check the position of HM and intrao- perative myocardial biopsies. The normal myocardium（NH） and the HM were obtained in operation. They were confirmed by electron microscope. P-ERK,P-p38 ,iNOS and GLUT4 were detected by western-blot. The relationship of P-ERK,P-p38 and iNOS,GLUT4 were also analyzed. Results P-ERK, P-p38 , GLUT4 and iNOS were significantly increased in HM compared with normal myocardium. There were positive correlation between P-ERK and GLUT4, between P-p38 and GLUT4, between P-p38 and iNOS. Conclusion ERK and p38 could be triggered by ischemia ,and actived ERK and p38 could promote the expression of GLUT4 and iNOS, promote the formation of HM.