小剂量异丙酚联合缺血后处理对豚鼠心肌缺血再灌注损伤的影响

Effects of small dose propofol combined with ischemic postconditioning on myocardial ischemia-reperfusion injury in guinea pigs

目的探讨小剂量异丙酚联合缺血后处理对豚鼠心肌缺血再灌注损伤的影响。方法24只白色雄性豚鼠，随机分为4组（n=6）：缺血再灌注组（I／R组）、异丙酚组（P组）、缺血后处理组（IPC组）和异丙酚＋缺血后处理组（P＋IPC组）。I／R组结扎左冠状动脉前降支30min，再灌注90min；P组自再灌注前5min至再灌注15min静脉输注异丙酚4mg·kg^-1·h^-1；IPC组心肌缺血30min，再灌注15s，缺血15s，反复4次，持续再灌注88min；P＋IPC组自再灌注前5min至再灌注15min静脉输注异丙酚4mg·kg^-1·h^-1，余同IPC组。记录缺血前和再灌注90min时左室收缩压（LVSP）、左室舒张末压（LVEDP）和左室压力变化速率（±dp／dtmax），计算左室发展压（LVDP=LVSP—LVEDP）；再灌注90min时取动脉血，测定血清肌酸激酶（CK）和乳酸脱氢酶（LDH）活性，取血后处死豚鼠，取心肌组织，测定心肌组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性。结果与I／R组比较，P＋IPC组再灌注90min时LVDP和±dp／dtmax升高，LVEDP降低，血清CK、LDH活性及心肌组织MDA含量减少，心肌组织SOD活性增加（P〈0．05），P组和IPC组上述指标差异无统计学意义（P〉0．05）。结论再灌注前5min至再灌注15min静脉输注异丙酚4mg·kg^-1·h^-1联合缺血后处理可通过抑制脂质过氧化反应，减轻豚鼠心肌缺血再灌注损伤。

Objective To investigate the effects of small dose propofol combined with ischemic postconditioning on myocardial ischemia-reperfusion （I/R） injury. Methods Twenty-four white male guinea pigs weighing 400-500 g were randomly divided into 4 groups （ n = 6 each） ： group Ⅰ I/R; group Ⅱ propofol （P） ; group Ⅲ ischemic postconditioning （IPC） and group Ⅳ P ＋ IPC. The animals were anesthetized with intraperitoneal 20% urethane 2 g/kg, intubated and mechanically ventilated. Myocardial I/R was produced by temporary occlusion of left anterior descending branch （LAD） of coronary artery for 30 min followed by 90 min reperfusion. In group P propofol was infused at 4 mg· kg^-1 · h^-1 from 5 min before reperfusion until 15 min of reperfusion. In group IPC the animals were subjected to 4 episodes of 15 second myocardial ischemia at 15 second intervals at the end of 30 min ischemia ; in group P ＋ IPC the animals received 20 min propofol infusion as in group P on top of the 4 episodes of 15 s myocardial ischemia as in group IPC. Left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP） and ± dp/dtmax were measured and recorded before ischemia and at the end of 90 min reperfusion. Serum creatine kinase （ CK ） and lactate dehydrogenase （ LDH ） activities and myocardial MDA content and SOD activity were determined at the end of 90 min reperfusion. Results The LVDP and ＋ dp/dtmax were significantly higher while LVEDP was significantly lower; the serum CK and LDH activities and myocardial MDA content were significantly lower while myocardial SOD activity was significantly higher at the end of 90 rain reperfusion in P ＋ IPC group （ group Ⅳ ） than in group I/R （ Ⅰ ） . Conclusion Small dose propofol combined with IPC can protect the heart against I/R injury through attenuating lipid peroxidation.