肝硬变大鼠肝缺血再灌注损伤的研究

STUDIES ON HEPATIC ISCHEMIA REPERFUSION INJURY IN RAT CIRRHOTIC LIVER

目的 研究肝硬变大鼠肝缺血再灌注 (hepaticischemiareperfusion ,HIR)后的损伤情况 ,寻找可耐受的缺血时限。方法 用 60 %四氯化碳 (CCl4 )溶液皮下注射的方法制作肝硬变大鼠模型。随机分为 4组 :A组 (假手术组 ,6只 ) ,B、C、D组分别为肝门完全阻断 2 0min、3 0min及 40min组 (每组各 16只 )。观察 4组大鼠 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)、肿瘤坏死因子 (TNF)及肝、肺病理的变化。结果 B、C、D组的 7天存活率分别为 10 0 %、60 %和 40 % ,C、D组与B组差异有统计学意义 (P <0 .0 5 )。再灌注后 4小时血清TNF含量 ,B、C、D组分别为 (0 .3 99± 0 .2 16)u/ml、(0 .671± 0 .3 5 1)u/ml和 (0 .789± 0 .3 71)u/ml ,明显高于术前的 (0 .177± 0 .13 9)u/ml(P <0 .0 1) ,且C、D组与B、A组比较 ,差异有统计学意义 (P <0 .0 5 )。再灌注 4小时后D组的AST、ALT分别为 (2 448.4±942 .3 )u/L、(1189.0 ±40 3 .4)u/L ,C组分别为 (2 185 .1±173 2 .9)u/L、(1183 .5 ±70 7.2 )u/L ,均明显高于B组、A组 ,差异有统计学意义 (P <0 .0 1)。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。结论 肝缺血再灌注损伤的程度随缺血时间的延长而加剧 ;在 2 0、3 0?

Objective To investigate the extent of hepatic ischemia reperfusion (HIR) injury in rat cirrhotic liver under different ischemic time,and find the time limit under which the rat with cirrhotic liver could tolerate. Methods At first,the cirrhosis of the rat were induced by carbon tetrachloride(CCl 4)injected subcutaneously. Then these rats were randomly divided into four groups. Group A(n=6) was made by sham operation, group B, C, D(n=16) were respectively given 20, 30, 40min hepatic warm ischemia. The 7-day survival rate, AST, ALT, TNF and liver, pulmonary pathology were observed. Results The 7-day survival rate was decreased with the increase of hepatic ischemic time. The survival rate of group B, C, D were respectively 100%, 60%, 40%. Between group C, D and group B there were significant differences(P<0.05). The level of AST and ALT in group D were (2 448.4±942.3)u/L and (1 189.0±403.4)u/L respectively, and those in group C were (2 185.1±1 732.9)u/L and (1 183.5±707.2)u/L respectively, which were higher than those in group B and A significantly(P<0.01). The level of TNF was increased significantly 4hr after reperfusion, as compared with that before operation 〔(0.177±0.139)u/ml〕, P<0.01. TNF of group B, C, D were (0.399±0.216)u/ml, (0.671± 0.351)u/ml and ( 0.789±0.371)u/ml respectively. At the same time the level of TNF in group C, D was higher than that in group B, A significantly(P<0.01). Liver and lung pathology showed increased damage with increasing ischemia. Conclusion Hepatic injury is induced by HIR in rats with cirrhotic liver, and its severity increases with the increase of ischemic time. There is a certain hepatic ischemic time between 20min and 30min, which can be tolerated by the rats with cirrhotic liver. TNF may be used as an indicator,showing the degree of HIR injury and foreseeing the result of injury.