缝隙连接阻滞剂对离体SD大鼠局部缺血心脏血流动力学的影响

目的 观察缝隙连接阻滞剂16-DSA对离体SD大鼠正常心脏及局部缺血心脏机械功能的影响,探索缝隙连接在维持心脏机械功能的作用.方法 建立离体SD火鼠心脏Langendorff灌流模型（含16-DSA的K-H灌流液）；结扎左前降支,建立局部心肌缺血模型；取缺血部分心肌进行免疫荧光染色检测,应用图像分析系统半定量分析细胞间机械连接和缝隙连接的代表蛋白,包括Desmoplakin和缝隙连接蛋白43（ Cx43）蛋白的水平.透射电镜观察缺血及16-DSA对心肌结构的影响.结果（1）16-DSA有使正常心脏左心室压最大上升速率（dp/dtmax）和左心室收缩峰压（LVSP）下降的趋势,对左心室舒张末压（LVEDP）无明显影响.局部缺血心脏的LVSP,dp/dtmax明显下降,LVEDP明显上升,16-DSA对缺血心脏的LVSP、dp/dtmax均无明显影响,对LVEDP有改善的趋势.（2）缺血心肌Cx43和Desmoplakin的表达面积比正常心肌明显减少.16-DSA可使缺血所致Cx43的减少发生部分逆转,但对Desmoplakin无明显影响.（3）通过透射电镜可见缺血对心肌细胞有破坏性影响,16-DSA可以减轻该影响.结论 （1）16-DSA可以使正常心脏的收缩功能下降,而对舒张功能无明显影响.（2）16-DSA可以部分逆转缺血对心脏舒张功能的破坏,可能与其部分逆转缺血对Cx43下调有关.但其对心肌机械连接——桥粒无明显影响.（3）16-DSA可以减轻由于缺血造成的心肌损害.

The effects of gap junction inhibitor on hemodynamics in isolated regional ischemic SD rat hearts

Objective To observe the effects of gap junction inhibitor 16-DSA on hemodynamics in normal and regional ischemic hearts of isolated SD rats,and to exploring the effects of gap junctions about it.Methods ( 1 )Establish the Langendorff perfusion model in SD rat,and perfused the SD rat heart with 16-DSA.Observe the effects of 16-DSA on the myocardial systolic and diastolic function.2.Establish the regional ischemic model by ligating the left anterior descending branch of coronary artery.Observe the effects of 16-DSA on the systolic and diastolic function.3.The protein expression of Cx43 and Desmoplakin in the sections of ischemic myocardium were evaluated by immunofluorescencet labeling method.3.Observe the influence of ischemia and 16-DSA on myocardium with transmission electron microscopy.Results ( 1 ) 16-DSA decreased dp/dtmax and LVSP,but had no effect on LVEDP in normal hearts.Ischemia decreased LVSP and dpmax/dt and increased LVEDP.16-DSA had no more influence on the downregulation of the systolic function by ischemia,and improved the diastolic function.(2)The level of Cx43 and DP protein evaluated by immunofluorescence microscopy in ischemic myocardium was lower than that in normal myocardium.16-DSA partially reverse the downregulation of Cx43,had no influence on the expression of DP.(3) Transmission electron microscopy revealed that 16-DSA lessened the damage of myocardium induced by ischemia.Conclusion ( 1 ) 16-DSA could decrease the systolic function of heart,but had no effect on diastolic function.(2) 16-DSA could partially reverse the damage of diastolic function by ischemia,which may due to its reversing of the Cx43 downregulation.3.16-DSA could lessen the damage of myocardium induced by ischemia.