缺血预处理时环磷酸腺苷含量及其依赖蛋白激酶活性的变化

Changes of the content of cyclic-AMP and activity of protein kinase A during the procedure of preconditioning

目的:应用大鼠在体缺血/再灌注模型,探讨心肌缺血预处理程序(PC)中环磷酸腺苷(cAMP)含量及cAMP依赖蛋白激酶(PKA)活性的变化及意义。方法:选择36只SD大鼠,进一步分为PC1-、2-、3-(缺血)组和PC1+、2+、3+(再灌注)组。用手术套管法造成左冠状动脉主干缺血及再灌注。损伤后取心脏用放射免疫法测cAMP水平,生化法测PKA活性变化。结果:心肌缺血预处理程序中cAMP含量及PKA活性随缺血及再灌注呈周期性波动。在5min缺血预处理时表现为反复明显增高,而在间隔的再灌注程序中恰呈相反改变,明显下降。再预处理程序中,5min缺血期相对于同一周期中的5min再灌注期,cAMP含量及PKA活性均有显著差异(P<0.01)。结论:cAMP及PKA的周期性波动变化可能是激发心肌缺血预适应(IP)的机制之一,cAMP可能在预处理保护作用中起重要作用。

Objective： To study changes of the content of cyclic-AMP （cAMP） and the activity of protein kinase A （PKA） during the procedure of preconditioning （PC） in rat myocardial in vivo. Methods： In this preconditioning procedure group, 36 SD rats were randomly further divided into PC1-, PC2-, PC3- group and PC1＋, PC2＋, PC3 ＋ groups, each group contained 6 rats. The 3 cycles of 5min ischemia were PC1-, PC2- and PC3-, the interval 5 min of interval reperfusion were PC1＋, PC2＋ and PC3＋. Rats received surgical preparation and underwent left coronary artery occlusion and reperfusion. After the procedures, the hearts were isolated. The activity of PKA was analyzed by method of biochemistry and the content of cAMP examined by radioimmunoassay （RIA）. Results： During the procedure of preconditioning, the content of cAMP and the activity of PKA varied with ischemia and reperfusion, presented marked fluctuation. Both indexes showed repeated significant increase when hearts exposed to three episodes of 5 min ischemia, and almost complete reversed by each reperfusion period, and had significant difference （ P〈0. 01） . Conclusion： The fluctuation of cAMP and PKA probably elicits the protection of ischemic preconditioning. Ischemie preconditioning can afford some protection to heart through myocardial cAMP content.