乳化异氟醚预处理对大鼠心肌缺血再灌注时NF—kB活性的影响

Effects of emulsified isoflurane preconditioning on myocardial NF-kB activity during ischemia-reperfusion in rats

目的 探讨乳化异氟醚预处理对大鼠心肌缺血再灌注时NF—kB活性的影响。方法健康雄性sD大鼠48只，体重230～280g，随机分为4组（n=12）：假手术组（s组）仅穿线不结扎；缺血再灌注组（IR组）结扎左冠状动脉前降支30min，恢复灌注120min制备心肌缺血再灌注损伤模型；脂肪乳剂组（L组）经股静脉输注30％脂肪乳剂4ml·kg^-1·h^-1 30min后制备模型；乳化异氟醚组（EI组）经股静脉输注乳化异氟醚4ml·kg^-1·h^-1 30min，洗脱15min后制备模型。于再灌注120min时采集股动脉血样，采用ELISA法测定血清心肌肌钙蛋白I（cTnI）、IL-6浓度及磷酸肌酸激酶同工酶（CK-MB）活性，随后处死大鼠取心脏，采用Westernblot法测定心肌细胞NF—xB活性，电镜下观察心肌细胞的超微结构。结果与s组比较，IR组、EI组和L组心肌细胞NF—kB活性升高，血清IL-6、cTnI浓度及CK-MB活性升高（P〈0．05或0．01）；与IR组比较，EI组心肌细胞NF-kB活性降低，血清IL-6、cTnI浓度及CK-MB活性降低（P〈0．05）；电镜结果显示：EI组心肌细胞损伤程度较IR组和L组减轻。结论乳化异氟醚预处理可通过降低NF-kB活性抑制炎性反应，从而减轻大鼠心肌缺血再灌注损伤。

Objective To investigate the effects of emulsified isoflurane preconditioning on myocardial NF-kB activity during ischemia-reperfusion （I/R） in rats. Methods Forty-eight healthy male SD rats weighing 230-280 g were randomly divided into 4 groups with 12 animals in each group： sham operation group （group S）, I/R group, lipid emulsion ＋ I/R group （group L） and emulsified isoflurane ＋ I/R group （group EI）. In group I/R, EI and L, myocardial I/R was produced by occlusion of left coronary anterior descending artery （LAD） for 30 rain followed by 120 rain reperfusion. In group L, 30% lipid emulsion 4 ml·kg^-1·h^-1 was infused intravenously for 30 min before myocardial I/R. In group EI, emulsified isoflurane 4 ml·kg^-1·h^-1 was infused intravenously for 30 min followed by 15 min washout before myocardial I/R. In group S and I/R, normal saline was given instead. Blood samples were taken from femoral artery at the end of 120 min reperfusion for determination of serum cTnI and IL-6 concentrations and CK-MB activity by ELISA. The rats were then killed and the myocardial tissues were taken for determination of NF-kB activity by Western blot and observation of the ultrastructure by electron microscopy. Results The NF-tcB activity, serum cTnl and IL-6 concentrations and CK-MB activity were significantly higher in group I/R, EI and L than in group S （ P 〈 0.05 or 0.01 ）, while lower in group EI than in group I/R （ P 〈 0.05 ）. Microscopic examination showed that emulsified isoflurane significantly attenuated the histopathological changes in group EI. Conclusion Emulsified isoflurane pretreatment can attenuate myocardial I/R injury through decreasing the NF-kB activity and inhibiting inflammatory response in rats.