缺血预处理和Caspase抑制剂对缺血再灌注损伤保护作用的比较

目的　比较缺血预处理和Caspase抑制剂治疗对大鼠肝缺血再灌注的保护作用及其机制。方法　SD大鼠随机分为 6组 :( 1)缺血再灌注1 (IR1 )组 ;( 2 )IR2 组 ;( 3 )缺血预处理1 (IP1 )组 ;( 4 )IP2 组 ;( 5 )Caspase抑制剂治疗1 (T1 )组 ;( 6)T2 组。比较各组大鼠 70 %肝脏 60min或 12 0min缺血 ,在再灌注 3h时的肝组织Caspase 3活性 ,肝细胞凋亡率和血清AST和ALT水平 ,及实验动物 7d存活率。结果　在 60min缺血及 3h再灌注时间 ,IP1 组和T1 组的保护作用相同 ,在 12 0min缺血及 3h再灌注时 ,T2 组对Caspase活性和肝细胞凋亡的抑制优于IP2 组 (P <0 .0 1) ,但两者的AST和ALT水平及动物 7d存活率均无显著性差异。结论　缺血预处理和Caspase抑制剂治疗对鼠肝缺血再灌注损伤都有保护作用 ,两者的保护效果无显著性差异。缺血预处理对缺血再灌注损伤的保护更简便、经济、安全 ,临床应用前景十分广阔。

Comparison of the protective effect of ischemic preconditioning and Caspase inhibitor on ischemia reperfusion injury of the liver in rats

Objective To compare the protective effect of ischemic preconditioning(IP) and caspase inhibitor on ischemia reperfusion(IR) injury of the liver in rats,and to investigate the possible mechanism. Methods SD rats subjected to 60 or 120 minutes of 70% hepatic ischemia and 3 hours of reperfusion,respectively,then divided randomly into 6 groups: (1)Ischemia/ reperfusion group 1 (IR 1 group);(2)IR 2 group;(3)Ischemia preconditioning group 1(IP 1 group);(4)IP 2 group; (5)Caspase inhibitor treatment group1(T 1 group);(6)T 2 group.Serum levels of aspartate aminotransferase (AST) and alanine aminotransfernase (ALT),and liver Caspase-3 activity, hepatocytes apoptosis,and animal seven-day(7 d) survive rate were determined. Results Both ischemic preconditioning and Caspase inhibitor treatment could protect the liver against IR injury,and their protective effect in IP 1 group and T 1 group was equally at 3h reperfusion after 60min ischemia. At 3h reperfusion after 120min ischemia, the effect of inhibiting Caspase-3 activity and decreasing hepatocyte apoptosis in T 2 group were significantly superior to those in IP 2 group(P<0.05),but the level of AST?ALT and 7-day surivvar rate were no significant difference between T 2 group and IP 2 group.(P>0.05). Conclusions Both IP and Caspase inhibitor treatment can protect the liver against IR injury in rats,and the protective effect is no significant difference between the two methods.However IP is more simple?safe and cheaper comparing with Caspase inhibitor treatment.