不同时限缺血预处理对硬化肝脏保护作用的实验研究

目的: 探讨缺血预处理对硬化肝脏缺血再灌注的作用,并寻找一种有效缺血预处理的时间窗和理想方案. 方法: 将64只雄性、肝硬化SD大鼠随机分为八组,每组八只:假手术组(SO组);缺血再灌注组(I/R组);缺血预处理1、2、3、4、5和6组(IPC1、IPC2、IPC3、IPC4、IPC5和IPC6).以肝组织ATP、ADP、AMP及EC(用高效液相色谱法测定),血清ALT、AST、LDH(用全自动生化仪测定)和肝脏胆汁分泌量来评价肝功能. 结果: 再灌注末,IPC3组、IPC4组、IPC5组ATP含量均明显高于I/R组(P分别为0.01、0.07和0.000);同样,测定EC时发现,IPC3组、IPC4组和IPC5组均明显高于I/R组(P=0.000).与I/R组比较,IPC4组和IPC5组的血清ALT差异有显著性(P分别为0.013和0.000);其血清LDH差异亦有显著性(P=0.023,P=0.000),而血清AST却只有IPC5组显著低于I/R组(P=0.001).IPC3组、IPC4组和IPC5组肝脏的胆汁分泌量明显高于I/R组(P=0.028,P=0.023,P=0.008). 结论: 5~10min予一次或两次缺血预处理,能启动IPC对肝硬化大鼠肝脏I/R损伤的保护作用;10 min的缺血预处理,对肝硬化大鼠肝脏I/R损伤的保护作用最强.

Protective effect of ischemic preconditioning in different periods on the liver cirrhosis in rats

Objective:To investigate the effects,the effective time window and the optimal scheme of IPC on cirrhotic liver of rat.Methods:Sixty four male SD rats with liver cirrhosis were divided into 8 groups randomly,eight rats in each group:sham operation(SO) group,ischemia reperfusion(IR) group,ischemic precontioning(IPC) 1,2,3,4,5 and 6 group. Hepatocellular viability was assessed by hepatic adenine nucleotide level and energy charge(EC) determined by HPLC, ALT?AST and LDH in serum mearsured by auto biochemistry analyzer and bile output.Results:At 120 min after reperfusion,the level of ATP and EC in IPC3?4 and 5 groups were significantly higher than that in I/R group. However,there was no significant difference between IPC1?2 and 6 groups and I/R group(P>0.05). ALT?LDH in serum in IPC4?IPC5 groups were significantly lower than those in IR group. Meanwhile,the increase in AST was prevented in IPC5 group. Bile output of ischemic liver in IPC3?4 and 5 groups was significantly higher than that in I/R group(P=0.028,P=0.023,P=0.008). However,there was no significant diffrence between IPC1?2 and 6 groups and IR group(P>0.05).Conclusion:The protective effect on the liver of cirrhotic rat can be stimulated by 5 to 10 min ischemia once or twice,then 5 min reperfusion preconditioning. Too short or too long period of ischemic preconditioning can not produce protective effect on the liver of cirrhotic rat. The optimal time window of IPC in cirrhotic liver is 10 min.