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

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

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220～280g，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％02—50％N1混合气体2h；TH组再灌注即刻吸入O2-M-CO2混合气体1h，调节气体浓度和呼吸频率，维持FiO250％、PaCO280～100mrnHg，而后继续吸人50％02—50％N1混合气体1h。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-KB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、PaO1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。

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 hyper capnia 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 mi- croscopic examination. The apoptotic index was calculated.Results MAP, PaO2 and PaCO2 were higher, and se- rum 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.