核因子抑制剂对心肺转流中心肌细胞ICAM-1表达的影响

Effects of NF-κB on expression of ICAM-1 of myocardium during cardiopulmonary bypass

目的探讨核因子抑制剂吡咯二硫氨基甲酸酯(PDTC)对心肺转流(CPB)中心肌细胞核因子-κB(NF-κB)p65和细胞间粘附分子-1(ICAM-1)活化的影响。方法12只犬随机分为PDTC组(P组)和对照组(C组),每组6只。P组于CPB转机前静脉注入PDTC 30 mg/kg,C组静脉注入等容量生理盐水。两组均全心缺血60 min,恢复灌注60 min。于CPB 5 min、阻断60 min及开放60 min时,用自制电钻取心肌组织,一部分置于30%甲醛溶液固定,制成石蜡切片,采用SABC法免疫组化染色,观察NF-κB p65及ICAM-1蛋白的表达情况,另一部分置于液氮中保存,用于测定组织中髓过氧化物酶(MPO)的含量。结果在CPB过程中,随着时间的延长NF-κB p65及ICAM-1蛋白表达逐渐增强,MPO的含量逐渐增多,而PDTC能减少其表达和组织中MPO的含量,组间比较差异有显著意义(P<0.05,P<0.01)。结论PDTC能抑制CPB过程中NF-κB p65及ICAM-1蛋白的表达,减少炎性细胞浸润。

Objective To observe the expression of NF-kB p65 and ICAM-1 in the myocardium during cardiopulmonary hypass（CPB）, and the effect of pyrrolidine dithiocarbamate （PDTC） on it in dogs. Methods Twelve adult hybrid healthy dogs were randomly divided into PDTC group （group P, n=6） and control group （group C, n=6）. All dogs were anesthesitized with 2.5% sodium pentobarhitone 25 mg/kg. After tracheal intuhation,PDTC 30 mg/kg was administered intravenously in group P, and same volume saline instead of PDTC in group C. Myocardial tissue was taken at 5 rain following CPB, 60 rain after aortic cross-clamping and 60 min after reperfusion for detecting the expression of NF-kB p65 and ICAM-1 protein, and for determining the activity of myeloperoxidase（MPO）. Results （1） At the end of CPB, the expression of NF-kB p65 in cardiac myocytes was significantly increased in group C than that in group P. Transiocation of p65 from cytoplasm to nucleus was also observed at 60 min after aortic cross-clamping and 60 min after reperfusion. （2） The expression of ICAM-1 in the myocardium was increased in both groups at 60 min after aortic cross-clamping, but was lower in group P than that in group C. （3） Myocardial MPO activity in group P was significantly lower than that in group C at 60 min after release of aortic clamping. Conclusion PDTC could reduce the inflammatory response by down-regulating NF-kB p65 and ICAM -1 expression during CPB.