脂肪乳预处理和后处理对大鼠心肌缺血/再灌注损伤的保护作用

目的 观察在心肌缺血/再灌注(I/R)损伤前(预处理)或损伤后(后处理)给予脂肪乳对心脏I/R损伤的改善作用,探讨脂肪乳在心脏保护方面的潜在价值.方法 实验采用大鼠Langendorff心脏离体灌流模型.将24只雄性SD大鼠随机分组:空白对照组(ISCH组)心脏离体平衡50 min,37 ℃缺血40 min,复灌120 min;脂肪乳预处理组(I-preC组)心脏离体平衡20 min,给予含30%的脂肪乳灌注液输注15 min,洗脱15 min,随后37 ℃缺血40 min,复灌120 min;脂肪乳后处理组(I-postC 组)心脏离体平衡50 min,37 ℃缺血40 min,复灌120 min,复灌开始即给予含30%的脂肪乳灌注液输注15 min.于平衡50 min和复灌120 min期间连续监测左室内压上升和下降最大速率(±dp/dt max)、左室舒张期末压(LVEDP)、左室舒张压(LVDP)、心率(HR).平衡20 min和复灌60 min时接取冠状动脉流出液,测定肌酸激酶(CK)和乳酸脱氢酶(LDH)的活性.复灌结束后计算心肌梗死面积.结果 心脏机械功能指标:与ISCH组比较,复灌期间I-postC组+dp/dt max、LVDP显著升高,-dp/dt max、LVEDP显著降低(P均＜0.05);而I-preC组各指标比较差异无统计学意义.冠状动脉生化指标:复灌60 min时I-preC组和I-postC组CK和LDH活性均较ISCH组显著降低(P均d＜0.05);I-preC组与I-postC组比较差异无统计学意义(尸均＞0.05).I-preC组和I-postC组心肌梗死面积较ISCH组显著降低[(21.6±1.8)%、(15.9±1.3)%比(46.5±3.9)%,P均<0.05)];I-preC组与I-postC组比较差异无统计学意义(P＞0v.05).结论 脂肪乳预处理和后处理均能减轻心肌I/R损伤后CK和LDH的释放,缩小心肌梗死面积.脂肪乳后处理能显著增强心肌I/R损伤后心脏的机械功能.

Protective effect of intralipid on myocardial ischemia/reperfusion injury in isolated rat heart

OBJECTIVE: To investigate whether intralipid could protect perfused hearts of rats against ischemia/reperfusion (I/R) injury when it was administered before (preconditioning) or after the adverse ischemic event (postconditioning), in order to ascertain if intralipid would be a novel therapeutic strategy for myocardial I/R injury. METHODS: Studies were conducted in Langendorff-perfused isolated rat hearts. Twenty-four male Sprague-Dawley (SD) rats were divided into 3 groups randomly. The experimental procedure consisted of balance perfusion for 50 minutes, warm global ischemia (37 centigrade) for 40 minutes and 120 minutes of reperfusion. Preconditioning of hearts in myocardial preconditioning (I-preC group) consisted of 15 minutes of intralipid followed by 15 minutes of wash out before ischemia for 40 minutes and reperfusion for 120 minutes. In myocardial postconditioning (I-postC group) rat hearts were perfused with intralipid for 15 minutes at the onset of reperfusion. Hearts without intralipid treatment served as ischemic control (ISCH) group. Left ventricular mechanical function [heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), maximal change rate of intraventricular pressure rise/down (+/-dp/dt max)] were measured during the experiment, cardiac enzyme activity [creatine kinase (CK), lactate dehydrogenase (LDH)] were determined at 20 minutes after balance and 60 minutes after reperfusion. RESULTS: Comparing with ISCH group, the LVDP and +dp/dt max in the I-postC group were significantly higher and LVDEP, -dp/dt max were lower when compared with ISCH groups during reperfusion (all P<0.05). There were no significant differences in above indexes in I-preC group. As compared with the ISCH group, the content of LDH and CK in I-preC and I-postC were significantly lower at 60 minutes after reperfusion (all P<0.05). However, there were no significant differences between the I-preC and I-postC groups with respect to the levels of LDH and CK. The infarct size (IS) of I-preC and I-postC was markedly smaller than that of the ISCH group at 120 minutes of reperfusion [(21.6+/-1.8)%, (15.9+/-1.3)% vs. (46.5+/-3.9)%, both P<0.05]. The IS did not differ between the I-preC and I-postC groups (P>0.05). CONCLUSION: Intralipid administered before or after ischemia can decrease the level of CK, LDH and IS during reperfusion in isolated rat hearts. Intralipid postconditioning improves mechanical function.