治疗性高碳酸血症对大鼠移植肝脏缺血再灌注损伤的影响

目的 探讨治疗性高碳酸血症对大鼠移植肝脏缺血再灌注损伤的影响.方法 清洁级雄性Wistar大鼠32只,6周龄,体重220～280 g,采用完全随机设计的方法两两配对实施肝脏原位移植16只.采用随机数字表法,将受体鼠随机分为2组(n=8):肝移植组(LT组)和治疗性高碳酸血症组(TH组).LT组再灌注即刻吸入50％ O2-50％N2混合气体2 h;TH组再灌注即刻吸入O2-N2-CO2混合气体lh,调节气体浓度和呼吸频率,维持FiO2 50％、PaCO2 80～ 100 mm Hg,而后继续吸入50％O2-50％N2混合气体lh.再灌注期间记录MAP、PaO2和PaCO2.再灌注2h时,取动脉血样,测定血清ALT、AST、TNF-α、IL-1和IL-6的水平；取肝组织,测定NF-κB活性,计算凋亡指数,观察肝组织病理学结果.结果 与LT组比较,TH组血清ALT、AST、TNF-α、IL-1和IL-6水平、肝组织NF-κB活性和凋亡指数降低,MAP、PaO2和PaCO2升高(P＜0.05).TH组肝组织病理学损伤较LT组减轻.结论 治疗性高碳酸血症可减轻大鼠移植肝脏缺血再灌注损伤,机制与抑制炎性反应和细胞凋亡有关.

Effect of therapeutic hypercapnia on hepatic ischemia-reperfusion injury in rat liver transplantation

Objective To investigate the effect of therapeutic hypercapnia on hepatic ischemia-reperfusion (I/R) injury in rat liver transplantation.Methods Male specific pathogen-free adult Wistar rats aged 6 weeks weighing 220-280 g were used in this study.Sixteen rats in which liver transplantation was successfully performed were randomly divided into 2 groups ( n =8 each): liver transplantation group (group LT) and therapeutic hypercapnia group (group TH).In group TH,PaCO2 was maintained at 80-100 mm Hg by inhalation of CO2 for 1 h at the begining of reperfusion.MAP,PaO2 and PaCO2 was recorded during reperfusion.Blood samples were obtained at 2 h of reperfusion for determination of serum ALT,AST,TNF-α,IL-1 and IL-6 levels,and then the rats were sacrificed and transplanted liver was immediately removed for determination of NF-κB activity and apoptosis and microscopic examination.The apoptotic index was calculated.Results MAP,PaO2 and PaCO2 were higher,and serum ALT,AST,TNF-α,IL-1 and IL-6 levels,NF-κB activity and apoptotic index lower in group TH than in group LT ( P ＜ 0.05).The histopathologic damage was ameliorated in group TH as compared with group LT.Conclusion Therapeutic hypercapnia can attenuate hepatic I/R injury in rat liver transplantation by inhibiting inflammatory response and apoptosis.