蛇床子素预处理对兔心肌缺血/再灌注损伤的保护作用研究

Study on the Protective Effect of Osthole Preconditioning for Myocardial Ischemia-Reperfusion Injury in Rabbits

目的:探讨蛇床子素预处理对兔急性心肌缺血/再灌注损伤的保护作用及其机制。方法:结扎新西兰大耳兔左冠状动脉前降支40 min后,松开结扎线再灌注120 min,制作急性心肌缺血/再灌注损伤模型。缺血/再灌注(I/R)组:缺血40 min,放松结扎线后再灌注120 min;缺血预处理(IPC)组:缺血5 min,再灌注5 min,反复3次,余处理方法同I/R组;蛇床子素预处理(Ost)组:缺血前30 min经耳缘静脉静注蛇床子素25 mg/kg,5 min内注完,余处理方法如I/R组。于实验结束时从右心室取血测定血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量及心肌肌钙蛋白(cTnI)、乳酸脱氢酶同工酶(LDH)、肌酸激酶(CK)、肌酸激酶同功酶(CK-MB)漏出率;采用TUNEL法原位标记缺血区凋亡心肌细胞并计算凋亡率。结果:各实验组血清SOD活性均较对照组高,MDA含量、cTnI及心肌酶(LDH、CK及CK-MB)漏出率均较对照组低(P<0.05);各实验组心肌细胞凋亡率均低于对照组(P<0.05)。结论:蛇床子素注射液预处理可减轻兔急性心肌缺血/再灌注损伤、减少心肌细胞凋亡,对心肌损伤可能有保护作用。

Objective： To study the protective effect and mechanism of osthole preconditioning to acute myocardial ischemia-reperfusion injury in rabbits. Methods： The model of acute myocardial ischemia-reperfusion injury was made after the left anterior descending branch of coronary artery of a New Zealand rabbit was occluded for 40 min and then reperfused with loosing the ligature for 120 min. Ischemia-reperfusion （I/R） group was occluded ischemia for 40 min and then reperfused for 120 min after loosing the ligature. Ischemic preconditioning （IPC） group was occluded ischemia for 5 min and then reperfused for 5 min, three cycles of myocardial ischemia （5min） and reperfusion （5min）. Other methods were the same as group I/R. Osthole preconditioning（Ost） group was injected osthole（25mg/kg） into the marginal ear vein within 5 min before 30 min of ischemia. Other methods were the same as group I/R. The leakage rate of serum superoxide dismutase （ SOD ）, malondialdehyde （ MDA ） contents, myocardial troponin I （ cTnI ）, lactate dehydrogenase （LDH）, creatine kinase（CK） and creatine kinase isoenzyme（CK-MB） was determined by collecting blood from right ventricle at the end of experiment. Apoptotic cardiacmyocyte in ischemic area was labeled by TUNEL method to calculate the apoptotic rate. Results：The activity of serum SOD in each experimental group was significantly higher than that in the control group. The leakage rate of MDA contents, cTnI and myocardial enzyme （ LDH, CK and CK-MB ） in each experimental group was lower than that in the control group （P 〈 0.05 ）. The myocardial apoptotic rate in each experimental group was lower than that in the control group （P 〈 0.05 ）. Conclusion ： Osthole injection preconditioning process may reduce the acute myocardial ischemia-reperfusion injury, decrease myocardial apoptosis and have a certain protective effect for myocardial injury in rabbits.