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.