吡咯二硫氨基甲酸酯对体外循环犬炎性反应及心肌能量代谢的影响

Effects of pyrrolidine dithiocarbamate on inflammatory response and myocardial energy metabolism in dogs during cardiopulmonary bypass

目的观察核转录因子抑制剂吡咯二硫氨基甲酸酯(PDTC)对体外循环犬炎性细胞因子及心肌能量代谢的影响。方法12只犬随机分为对照组(C组)和PDTC组(P组),每组6只。P组于CPB前静脉注射PDTC 30 mg/kg,C组静脉注入等量生理盐水。全心缺血60 min,灌注60 min。分别于阻断升主动脉前(基础值)、阻断升主动脉后30、60 min及开放升主动脉后30、60 min测定血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)浓度;于阻断升主动脉前、阻断升主动脉后60min及开放升主动脉后60min取心肌组织,测定ICAM-1表达及腺苷酸(ATP、ADP、AMP、TAN、EC)含量。结果1. TNF-α浓度:两组在阻断升主动脉后各时点TNF-α浓度均高于基础值(P<0.01),P组低于C组(P< 0.01)。2.IL-1β浓度:C组在阻断后各时点高于基础值(P<0.01),P组在阻断升动脉后各时点均未见升高;P组低于C组(P<0.01)。3.心肌ICAM-1表达:阻断前两组均未见ICAM-1表达,随着CPB时间的延长,两组ICAM-1表达均增强(P<0.01),但P组弱于C组(P<0.05)。4.心肌腺苷酸含量:与基础值比较,两组阻断升主动脉后ATP、TAN及EC含量均降低,开放升主动脉后C组ATP、TAN及EC降低,P组ATP降低(P<0.05或0.01),TAN和EC差异无统计学意义(P>0.05);P组高于C组(P< 0.05或0.01)。结论PDTC可抑制CPB所致的炎性反应,减缓心肌高能磷酸盐的降解。

Objective To investigate the effects of pyrrolidine dithiocarbamate （PDTC） on plasma concentrations of proinflammatory cytokines and myocardial energy metabolism induced by cardiopulmonaxy bypass （CPB）. Methods Twelve healthy mongrel dogs of both sexes weighing 13.5-17.5 kg were randomly divided into 2 groups （ n = 6 in each group） ： PDTC group and control group. The animals were anesthetized with intraperitoneal 2.5 % pcntobarbital sodium 25 mg· kg^- 1 , intubated and mechanically ventilated. In PDTC group PDTC 30 mg·kg^- 1 was given i.v. after tracheal intubation while in control group normal saline was given instead of PDTC. Aorta was clamped for 60 min and then unclamped for 60 min repcrfusion during CPB. Blood samples were taken before（baseline）, 30 and 60 min after aortic clamping and 30 and 60 min after aortic unclamping for determination of plasma concentrations of TNF-α and IL-1β. Myocardial tissue was obtained before and 60 min after aortic clamping and 60 min after aortic unclamping for determination of myocardial content of adenine nucleotide （ ATP, ADP,AMP, TAN, EC） and expression of ICAM-1 protein. Results Plasma TNF-α concentration was increased after aortic cross-clamping as compared to the baseline value before clamping in both groups but the TNF-α concentration was significantly lower in PDTC group than in control group （P 〈 0.01）. Plasma IL-1β concentration increased significantly after aortic cress-clamping as compared to the baseline value in control group whereas no significant increase in IL-1β concentration was found in PDTC group. The expression of ICAM-1 in myocardium was significantly increased after aortic cross-clamping in both groups but was significantly lower in PDTC group than in control group （P 〈 0.05）. The myocardial content of ATP was decreased after aortic cress-clamping as compared to the baseline value in both groups. The recovery of ATP content was significantly better in PDTC group than in control group. Similar changes in myocardial TAN and EC content were also found. Conclusion Pretreatment with PDTC is effective in reducing CPB-induced inflammatory response and changes in myocardial energy metabolism.