异丙酚对糖尿病大鼠缺血再灌注心肌NF-κB、TNF-α和IL-6的影响

Effects of propofol on inflammatory response induced by myocardium ischemia /reperfusion in diabetic rats

目的探讨异丙酚对糖尿病缺血再灌注心肌保护作用机制。方法健康雄性SD大鼠100只,随机分为糖尿病组76只(76只大鼠造模成功60只)和非糖尿病组24只。非糖尿病大鼠随机分为假手术组(Ⅰ组)和缺血再灌注组(Ⅱ组);60只糖尿病大鼠随机分为假手术组(Ⅲ组)、缺血再灌注组(Ⅳ组)和异丙酚低(Ⅴ组)、中(Ⅵ组)、高(Ⅶ组)剂量组,每组12只。记录缺血前、缺血30 min、再灌注120 min时心率(HR)、平均动脉压(MAP),并计算心率-血压指数。ELISA测定血清及心肌组织TNF-α、IL-6的含量。免疫组化染色分析心肌组织中NF-κB的核移位,Westernblotting检测心肌组织NF-κB的表达量。结果与Ⅰ组比较,Ⅲ组缺血前HR、MAP及血压-心率指数降低(P<0.05或<0.01);与Ⅱ组比较,Ⅳ组,HR、MAP及血压-心率指数降低(P<0.05或<0.01),血清及心肌组织TNF-α、IL-6含量明显升高(P<0.05),NF-κB活化,明显从细胞浆移位于细胞核,表达量也显著增加;与Ⅳ组比较,缺血再灌注后,Ⅵ组、Ⅶ组HR、MAP及血压-心率指数改善(P<0.05或<0.01),血清、心肌组织中TNF-α、IL-6含量明显降低。结论应用异丙酚后能明显抑制糖尿病心肌I/R后NF-κB的活化和TNF-α、IL-6的表达增加,心功能明显改善。

Objective To explore the molecular mechanisms of propofol in cardioprotection by means of ischemia/reperfusion injury model in diabetic rats. Methods A total of 100 SD rats were randomly divided into two groups ： non-diabetes group （ n = 24） and diabetes group （ n = 76）. Finally, 60 diabetic rat models were successfully established. The rats in non-diabetes group were randomly redivided into sham-operation group （ I ）, I/R group（ II ）, then the rats in diabetes group were randomly redivided into sham-operation group （ i ）, I/R group （IV） and propofol 3,6,12mg kg-1 h-1（ V, VI, VII） groups, with 12 rats in each group. Heart rate （HR） ,mean arterial blood pressure （MAP） and blood pressure/heart rate index （PRI） were recorded during occlusion and at the end of reperfusion, respectively. The concentrations of TNF-α, IL-6,in serum and myocardium were detected by ELISA. The translocation of NF-KB in the cardiomyocytes was determined by immunohistochemistry,and the expression levels of NF-KB were detected by Western Blot. Results As compared with those in group I , before ischemia the cardiac function parameters （ HR, MAP, PRI） were obviously decreased in group m （ P 〈 o. 05 or 〈 0.01 ）. However the concentrations of TNF-α, IL-6 in serum and myocardium, the expression levels of TNF-α,IL-6 mRNA in myocardium of groupIV were significantly higher than those of group II （ P 〈0.05 or 〈0.01 ）. The expression levels of NF-KB in nuclei in group IV were markedly higher than those in group III（ P 〈0.01）. As compared with those in group IV,administration of propofol at 6,12mg kg-1 h-1 significantly inhibited the NF-KB to translocate into nucleus and decreased the expression of NF-KB in the nuclei （P 〈 0.05）, and reduced the concentrations of TNF-α, IL-6 in serum and myocardium, respectively （ P 〈 0.05 or 〈 O. O1 ）. Conclusion Propofol can markedly inhibit NF-KB activation in myocardium after I/R in diabetic rats,which can also increase the expression levels of TNF-α and IL-6, as a result, which can obviously improve cardiac function.