甘氨酸对离体缺血再灌注大鼠心脏的保护作用

Protective Effects of Glycine on Isolated Rat Hearts against Injury Induced by Ischemia Reperfusion

目的探讨甘氨酸对离体大鼠心脏缺血再灌注引起的心脏损伤的拮抗作用及其机制。方法采用Langen-dorff心脏灌流技术。正常对照组持续灌流90 min;缺血再灌注组平衡30 min,停灌30 min,再灌30 min;甘氨酸组从停灌前15 min开始加入3 mmol/L甘氨酸,其他同缺血再灌注组。结果甘氨酸处理使缺血再灌注所致心律失常持续时间缩短85%,丙二醛(MDA)含量降低61%,心肌凋亡细胞减少65%,Bcl-2表达增加140%,Bax表达减少68%。结论甘氨酸减轻缺血再灌注损伤引起的心肌细胞凋亡,此作用可能与其抗自由基、调节Bcl-2和Bax的表达有关。

Objective To investigate the anti-injury effect of glycine in perfused rat hearts and the mechanism.Methods Isolated rat hearts were perfused in Langendorff mode.The hearts in normal group was perfused for 90 min.In the ischemia-reperfusion(IR) group,after stabilization for 30 min the injury was induced by 30 min global ischemia followed by 30 min reperfusion.In glycine group,the same protocol as the IR group was done except that 3 mmol/L glycine was given 15 min before ischemia and throughout reperfusion.Electrocardiogram(ECG) was monitored.Myocardial malondialdehyde(MDA) content was measured.Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL) method.The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry.Results Ischemia-reperfusion elicited arrhythmia,increased myocardial MDA content and apoptosis significantly,meanwhile,it upregulated the overall expression of Bcl-2 and Bax protein.Compared with IR group,glycine shortened arrhythmia lasting time(3±2 min vs 20±9 min),decreased myocardial MDA content(1.5±0.6 vs 3.8±(1.2),) reduced myocyte apoptosis \,upregulated the Bcl-2 expression(24.4±1.0 vs 10.0±2.3) and downregulated the Bax expression(12.4±1.8 vs 39.2±5.8).Conclusion Glycine inhibits the apoptosis of cardiac myocytes via reducing oxidative stress,upregulating Bcl-2 and downregulating Bax proteins.