七氟醚预处理对心肌缺血再灌注损伤大鼠血清NF-κB、TNF-α、IL-6表达的影响

Effects of sevoflurane preconditioning on the expression of serum NF-κB,TNF-α and IL-6 in rats model of myocardial ischemia-reperfusion injury

目的探究七氟醚(SEVO)预处理对心肌缺血再灌注损伤大鼠血清核因子(NF-κB)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)表达的影响。方法雄性SD大鼠70只,随机分为7组(n=10):(1)Shame组(假手术组)。(2)I/R组(单纯缺血再灌注组)。(3)BW1组:缺血前注射NF-κB特异性激动剂灰树花β-葡聚糖BW1 1.0 mg/kg,30 min后进行缺血再灌注。(4)SEVO+NO组:缺血前先吸入SEVO 30 min后,停止吸入165 min,不进行缺血再灌注。(5)SEVO组:缺血前30 min吸入SEVO维持30 min。(6)BW1+SEVO组:缺血前先注射BW1,30 min后,吸入SEVO。(7)SEVO+BW1组:缺血前先吸入SEVO 30 min后,立即注射BW1。对于SEVO处理组,SEVO持续吸入30 min后,停止吸入15 min以排除SEVO,心肌缺血30 min后,再灌注2 h。比较各组麻醉后即刻、吸入SEVO 15 min、缺血前、缺血15 min、再灌注1 h、再灌注2 h时的心率(HR)、平均动脉压(MAP)、收缩压与心率的乘积(RPP)情况。采用三苯基四唑氯化物(TTC)染色法测定心肌危险区域梗死面积和梗死区域面积。30只大鼠随机分为3组,每组10只,Shame组、I/R组、SEVO组大鼠处理同上。再灌注2 h后,腹主动脉取血,采用放射性免疫法分别测各组血清NF-κB、TNF-α、IL-6水平。结果吸入SEVO 15 min时,SEVO-NO组、SEVO组、BW1+SEVO组、SEVO+BW1组的HR、MAP、RPP水平均显著低于麻醉后即刻水平(P<0.05)。各组危险区面积差异无统计学意义(P>0.05)。与I/R组相比,SEVO组和BW1+SEVO组梗死区面积显著减小(P<0.05);与SEVO组相比,SEVO+BW1组梗死面积显著增加(P<0.05)。与Shame组相比,I/R组NF-κB、TNF-α、IL-6水平显著增加(P<0.05);与I/R组相比,SEVO组NF-κB、TNF-α、IL-6水平显著下调(P<0.05)。结论七氟醚预处理,可减少大鼠心肌缺血再灌注后梗死面积,保证血流动力学稳定,并通过抑制NF-κB信号通路活性来抑制TNF-α、IL-6分泌,保护心脏以免于受缺血再灌注的损伤。

Objective To investigate the effects of sevoflurane preconditioning on the expression of serum NF-κB,TNF-α and IL-6 in rats with myocardial ischemia-reperfusion injury. Methods 70 male SD rats were randomly divided into 7 groups（ n = 10） ：（1）Shame group（ sham operation group）.（2）I/R group（ simple ischemia-reperfusion group）.（3）BW1 group received BW1（ NF-κB activitor） 1. 0 mg/kg iv before I/R.（4）SEVO ＋ NO group received SEVO and no ischemia and reperfusion.（5）SEVO group inhaled 2. 5% sevoflurane for 30 min followed by15 min wash-out before I/R.（6）BW1 ＋ SEVO group received BW1 1. 0 mg/kg before SEVO inhalation.（7）SEVO ＋ BW1 group received BW1 1. 0 mg/kg after SEVO inhalation. For SEVO treatment group,SEVO continued to inhale for 30 min,stop breathing for 15 min to exclude SEVO,myocardial ischemia 30 min,reperfusion 2 h. The heart rate（ HR）,mean arterial pressure（ MAP）,systolic blood pressure multiplied heart rate（ RPP） situation were compared between each group immediately after anesthesia,inhaled SEVO 15 min,before ischemia,15 min after ischemia,1 h after reperfusion,and 2 h after reperfusion. The myocardial infarct area in dangerous area and infarct area was measured by TTCstaining. 30 rats were randomly divided into 3 groups（ n = 10） ： Shame group,I/R group and SEVO group. The rats were treated with the same method. After2 hours of reperfusion,the abdominal aorta was taken and the radioimmunoassay Serum levels of NF-κB,TNF-α and IL-6 were measured.Results When inhaled SEVO 15 min,the levels of HR,MAP and RPP in group SEVO-NO,SEVO,BW1 ＋ SEVO and SEVO ＋ BW1 were significantly lower than those immediately after anaesthesia（ P〈0. 05）. There were no significant difference in dangerous size among each group（ P〈0. 05）. Compared with I/R group,the area of infarct size in SEVO group and BW1 ＋ SEVO group were significantly decreased（ P〈0. 05）.Compared with SEVO group,the infarct size of SEVO ＋ BW1 group was significantly increased（ P〈0. 05）. Compared with the Shame group,the levels of NF-κB,TNF-α and IL-6 in the I/R group were significantly increased（ P〈0. 05）. Compared with the I/R group,NF-κB,TNF-α and the level of IL-6 were significantly down（ P〈0. 05）. Conclusion Sevoflurane preconditioning can reduce the infarct size after myocardial I/R in rats,ensure hemodynamic stability,and inhibit the secretion of TNF-α and IL-6 by inhibiting the activity of NF-κB signaling pathway,protecting the heart against I/R injury.