不同浓度硝酸甘油对大鼠离体心脏缺血再灌注损伤的影响

目的 探讨不同浓度硝酸甘油对大鼠离体心脏缺血再灌注损伤的影响.方法 健康成年雌性SD大鼠,体重220～330 g,周龄7周,建立Langendorff离体心脏灌注模型,取模型制备成功的心脏30个,随机分为3组(n=10):缺血再灌注组(IR组)K-H液灌注15 min,停灌20 min,再灌注60 min;低浓度硝酸甘油组(LN组)采用含有2.5 μg/L硝酸甘油的K-H液灌注15 min,停灌20 min,再灌注60 min;高浓度硝酸甘油组(HN组)采用含有25μg/L硝酸甘油的K-H液灌注15 min,停灌20 min,再灌注60 min.于再灌注10、20、30、40、50、60 min时记录心率(HR)、冠状动脉流量(CF)、左心室舒张末压(LVEDP)、左心室发展压(LVDP)、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dt_(max)).于平衡灌注末、再灌注5、30和60 min时收集冠状动脉流出液1.5 ml,测定乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性;于再灌注60 min时取心脏,测定心肌梗死面积,计数心肌凋亡细胞.结果 与IR组比较,LN组HR、CF、LVDP,+dp/dt_(max)和-dp/dt_(max)升高,LVEDP、CK活性、LDH活性、心肌梗死面积和细胞凋亡率降低(P<0.05),HN组HR、CF、LVDP、+dp/dt_(max)和-dp/dt_(max)降低,LVEDP、CK活性、LDH活性、心肌梗死面积和细胞凋亡率升高(P<0.05).与LN组比较,HN组HR、CF、LVDP、+dp/dt_(max)和-dp/dt_(max)降低,LVEDP、CK活性、LDH活性、心肌梗死面积和细胞凋亡率升高(P<0.05).结论 低浓度硝酸甘油(2.5μg/L)可减轻大鼠离体心脏缺血再灌注损伤,而高浓度硝酸甘油(25 μg/L)则可加重心脏缺血再灌注损伤.

Effects of different concentrations of nitroglycerin on ischemia-reperfusion injury in isolated rat hearts

Objective To investigate the effects of different concentrations of nitroglycerin on ischemia-reperfusion (IR) injury in the isolated rat hearts. Methods Healthy adult male SD rats 7 weeks old weighing 220-330 g were anesthetized with intraperitoneal pentobarbital 50 mg/kg. Their hearts were excised and perfused in a Langendorff apparatus. Thirty isolated hearts were randomly divided into 3 groups (n = 10 each) : group 1R, low-concentration nitroglycerin group (group LN) and high-concentration nitroglycerin group (group HN). The hearts in group IR were perfnsed with plain modified K-H solution. The hearts in group LN were perfused with K-H solution containing nitroglycerin 2.5 μg/L. The hearts in group HN were perfnsed with K-H solution containing nitroglycerin 25 μg/L. After 15 min of post-preparation equilibration, IR was induced by 20 min suspension of perfusion followed by 60 min reperfusion. HR, left ventricular end-diastolic pressure (LVEDP), coronary flow (CF), left ventricular developed pressure (LVDP), + dp/dtmax, and - dp/dtmax were measured at 10, 20, 30, 40, 50 and 60 min of reperfusion. To determine the activities of myocardial lactate dehydrogenase (LDH) and creatine kinase (CK), 1.5 ml of coronary effluent was collected at the end of equilibration, and at 5, 30 and 60 min of reperfusion. At 60 min of reperfusion, myocardial tissues were obtained to determine myocardial infarct size (IS) (by Trc staining) and assess the apoptosis rate (by TUNAL technique) .Results Compared with group IR, HR, CF, LVDP, + dp/dtmax and - dp/dtmax were significantly increased in group LN, while significantly decreased in group HN, and LVEDP, activities of CK and LDH in the coronary effluent, myocardial IS and apoptosis rate were significantly decreased in group LN, while significantly increased in group HN (P < 0.05). Compared with group LN, HR, CF, LVDP, + dp/dtmax and - dp/dtmax were significantly decreased, and LVEDP, activities of CK and LDH in the coronary effluent, myocardial IS and apoptosis rate significantly increased in group HN (P < 0. 05). Conclusion Low-concentration nitroglycerin can attenuate myocardial IR injury in isolated rat hearts, but high-concentration nitroglycerin can exacerbate the injury.