肝缺血再灌注对肝硬化大鼠的损伤作用

Injurious effects of hepatic ischemia/reperfusion on cirrhotic rat liver

目的 研究肝硬化大鼠肝缺血再灌注 (hepaticischemiareperfusion ,HIR)损伤的机制和程度。方法 用 6 0 %四氯化碳 (CCl4)溶液皮下注射的方法制作肝硬化大鼠模型。肝硬化大鼠随机分为六组 :A组 :假手术组 (6只 ) ;B、C、D组 :分别为肝门完全阻断 2 0min、30min、4 0min(每组各 16只 ) ;E组 :单纯肠系膜上静脉阻断 (16只 ) ;F组 :肝门阻断 +门腔转流 (16只 ) ;另外 ,随机取 10只正常肝脏大鼠组成G组 ,行肝门完全阻断 30min。观察 7天存活率、丙氨酸氨基转移酶 (ALT)、天门冬氨酸氨基转移酶 (AST)、透明质酸 (HA)、肿瘤坏死因子 (TNF) ,以及肝、肺病理的变化。结果 B、C、D、E、F、G组的 7天存活率分别为 10 / 10只、6 / 10只、4 / 10只、5 / 10只、8/ 10只、6 / 10只 ;再灌注后 4h血清TNF变化 :后六组均明显高于术前 ,C、D组高于B、A组 ,E、F组也明显高于A组 (P <0 0 1)再灌注 4h后HA变化 :D组明显高于B、E组 ,F、C组明显高于A组 (P <0 0 5 ) ;再灌注 4h后D、C组的AST、ALT均明显高于B组、A组 ,D组的AST明显高于F组 ,F组的AST、ALT显著高于E组 (P <0 0 5 ) ;C、G两组比较 ,上述指标的差异无显著性 (P >0 0 5 ) ;肝、肺组织学检查可见肝、肺的病理损害 ,程度随缺血时间的延长而加重 ,E组损伤重?

Objective To investigate the extent and mechanism of hepatic ischemia reperfusion (HIR) in cirrhotic rat liver. Methods The model of liver cirrhosis was established by subcutaneous injection of carbon tetrachloride (CCl 4) in 86 rats. Then the rats were randomized into 6 groups. In group A (n=6), sham operation was performed. In groups B, C and D with 16 rats in each, hepatic warm ischemia was achieved for 20, 30 and 40 min, respectively. In group E (n=16), only the superior mesenteric vein was occluded for 40 min. In group F (n=16), extracorporeal portosystemic shunt from portal vein to inferior vena cava was performed to avoid portal venous congestion during Pringle's maneuver for 40 min. Meanwhile, hepatic warm ischemia for 30 min was given to a total of 10 normal rats (Group G). The 7 day survival rate and changes in AST, ALT, HA, TNF, liver histology and pulmonary histology were observed. Results The 7 day survival rate was 100%, 60%, 40%, 50%, 80% and 60% in groups B, C, D, E, F and G, respectively. In group B, the level of TNF was significantly increased 4 h after the reperfusion (P<0 01). The level of TNF was markedly higher in groups C and D than in groups B and A (P<0 05). In addition, it was remarkably higher in groups E and F than in group A (P<0 05). In 4 h after the reperfusion, HA was significantly higher in group D than in groups B and E (P<0 05). It was markedly higher in groups C and F than in group A (P<0 05). The levels of AST and ALT in groups C and D were markedly higher than those in groups B and A (P<0 05). The level of AST was remarkably higher in group D than group F while those of AST and ALT were higher in group F than in group E (P<0 05). There were no significant differences in the above mentioned indexes between group C and group G (P>0 05). Pathological changes were seen in the liver and lungs. The injury aggravated along with prolongation of ischemia. Conclusions Many organs are involved during HIR injury in cirrhotic rat liver. The maximal tolerable hepatic ischemic time is 30 min.