【摘要】 目的探讨缺血预适应(ischemic preconditioning,IPC)对老年大鼠缺血-再灌注损伤(I/R)后心肌的影响。方法取Wistar大鼠56只,其中21~23月龄(老年鼠)和4~5月龄(青年鼠)各28只,建立离体心脏Langendorff灌注模型,按随机数字表法分为7组(每组8只):青年对照组、青年I/R组、青年IPC组、老年对照组、老年I/R组、老年IPC组、老年强化IPC组。对照组采用全心灌流90 min,不做任何处理;I/R组采用心脏平衡灌流30min后,缺血30 min,再复灌30 min;IPC组采用心脏平衡灌流10 min,经2次缺血5 min再灌注5 min后,缺血30min,再复灌30 min;强化IPC组采用心脏平衡灌流10 min,经4次缺血5 min再灌注5 min后,缺血30 min,再复灌30min。比较各组复灌30 min后心排血量(CO)的恢复率、左心室发展压(LVDP)、左心室内压最大上升和下降速率(±dp/dtmax)的恢复率;检测缺血前及复灌30 min后冠脉流出液中肌酸激酶(CK)的活性、心肌组织中丙二醛(MDA)和超氧化物歧化酶(SOD)的含量;比较各组心肌梗死范围。结果复灌30 min后青年IPC组与青年I/R组比较,CK生成明显减少(89.48±18.72 U/L vs.115.76±16.72 U/L,q=6.061,P<0.01),MDA含量明显降低(9.53±3.44 nmol/ml vs.16.84±2.29 nmol/ml,q=7.732,P<0.01),SOD含量明显增加(584.70±122.62 U/mlvs.429.46±85.24 U/ml,q=4.754,P<0.01),CO,LVDP,+dp/dtmax,-dp/dtmax恢复率明显增加(78.69%±9.68%vs.65.10%±8.63%,83.61%±8.46%vs.67.23±8.68%,81.68±8.68%vs.67.89%±6.89%,89.79%±7.78%vs.66.79%±8.46%,P<0.01),心肌梗死范围明显减小(5.25%±4.33%vs.14.75%±8.02%,q=7.458,P<0.01)。老年IPC组与I/R组上述指标比较差异无统计学意义(P>0.05),而老年强化IPC组与I/R组比较差异有统计学意义,复灌30 min后CK生成明显减少(88.60±28.32 U/L vs.105.76±9.64 U/L,q=5.620,P<0.01),MDA含量明显降低(8.38±3.36 nmol/ml vs.16.80±3.06 nmol/ml,q=7.500,P<0.01),SOD含量明显增加(558.87±78.66 U/ml vs.433.75±86.65 U/ml,q=7.335,P<0.01),CO,LVDP,+dp/dtmax,-dp/dtmax恢复率明显增加(77.99%±10.02%vs.66.26%±9.78%,85.59%±6.67%vs.73.90%±6.66%,83.87%±9.98%vs.68.90%±8.68%,86.01%±7.66%vs.70.39%±7.98%,P<0.01),心肌梗死范围明显减小(7.95%±6.32%vs.15.68%±10.36%,q=8.680,P<0.01)。结论IPC对老年大鼠I/R心肌保护作用减弱,强化IPC可以恢复IPC对老年大鼠I/R心肌保护作用。更多还原

【Abstract】 Objective To investigate the effect of ischemic preconditioning(IPC) on myocardial ischemic reperfusion injury(I/R) of elderly rats. Methods Fifty-six Wistar rats,of which there were 28 aged from 21-23months(elderly rat) and 28 aged from 4-5months(young rat),were used to build isolated heart perfusion Langendorff model.The rats were divided into 7 groups with random number table(8 in each group): adult control group,adult I/R group,adult IPC group,elderly control group,elderly I/R group,elderly IPC group and elderly enhanced IPC group.The control group underwent a 90-min perfusion without any intervention;the I/R group underwent a 30-min equilibration period,then a 30-min ischemia and a 30-min reperfusion;the IPC group underwent a 10-min equilibration period,then a 5-min ischemia for twice and a 5min reperfusion,after that a 30-min ischemia and a 30-min reperfusion;the enhanced IPC group underwent a 10-min equilibration period,then a 5-min ischemia for 4 times and a 5-min reperfusion,after that a 30-min ischemia and a 30-min reperfusion.The recovery rates of cardiac output(CO),left ventricular developed pressure(LVDP),the maximum rising and descending rate of left ventricular pressure(±dp/dtmax) after a 30-min reperfusion were compared among groups.The activity of creatine kinase(CK) in coronary outflow,the level of malonyldialdehyde(MDA) and superoxide dismutase(SOD) before ischemia and after a 30-min reperfusion were detected.The myocardial infarction areas were compared among groups.Results After a 30-min reperfusion,compared with adult I/R group,in adult IPC group CK reduced significantly(89.48±18.72 U/L vs.115.76±16.72 U/L,q=6.061,P<0.01),the level of MDA decreased significantly(9.53±3.44 nmol/ml vs.16.84±2.29 nmol/ml,q=7.732,P<0.01),the level of SOD increased significantly(584.7±122.62 U/ml vs.429.46±85.24 U/ml,q=4.754,P<0.01),the recovery rates of CO,LVDP,+dp/dtmax and-dp/dtmax increased significantly(78.69%±9.68% vs.65.10%±8.63%,83.61%±8.46% vs.67.23±8.68%,81.68±8.68% vs.67.89%±6.89%,89.79%±7.78% vs.66.79%±8.46%,P<0.01),the myocardial infarction areas reduced significantly(5.25%±4.33% vs.14.75%±8.02%,q=7.458,P<0.01).There was no statistical significance between elderly IPC group and elderly I/R group in the above indexes(P>0.05).However,There was statistical significances between elderly enhanced IPC group and I/R group.CK reduced significantly(88.60±28.32 U/L vs.105.76±9.64 U/L,q=5.620,P<0.01),the level of MDA decreased significantly(8.38±3.36 nmol/ml vs.16.80±3.06 nmol/ml,q=7.500,P<0.01),the level of SOD increased significantly(558.87±78.66 U/ml vs.433.75±86.65 U/ml,q=7.335,P<0.01),the recovery rates of CO,LVDP,+dp/dtmax and-dp/dtmax increased significantly(77.99%±10.02% vs.66.26%±9.78%,85.59%±6.67% vs.73.90%±6.66%,83.87%±9.98% vs.68.90%±8.68%,86.01%±7.66% vs.70.39%±7.98%,P<0.01),the myocardial infarction areas reduced significantly(7.95%±6.32% vs.15.68%±10.36%,q=8.680,P<0.01).Conclusion The protective effect of IPC on I/R elderly rat hearts has weakened.The enhanced IPC is able to regain the protective effect of IPC on elderly rat hearts.更多还原