鼠肝缺血再灌注损伤Caspase3活性变化及缺血预处理的保护机制

Caspase 3 Activity of Ischemia Reperfusion Injury in Rats and The Protective Mechanism of Ischemic Preconditioning

目的 探讨天冬氨酸特异性半胱氨酸蛋白酶 (Cystene -requiringaspartateprotease ,Caspase)在鼠肝缺血再灌注 (IschemicReperfusion ,IR)损伤中的变化及缺血预处理 (IschemicPreconditioning ,IP)的保护作用机制。方法 3 0只大鼠随机分为IR组、IP组及假手术组 (S)组。检测再灌注术后 3h血清AST、ALT水平、肝组织caspase3活性、肝细胞凋亡指数 (ApoptosisIndex ,AI)和电镜下超微结构改变。结果 ⑴血清AST、ALT改变 :IP组和IR组较S组显著升高 (P <0 0 1) ,其中IR组升高最明显 ,与IP组比较差异有显著性 ( P <0 0 1)。⑵肝组织Caspase3活性 ,IR组和IP组较S组明显升高 ( P <0 0 1) ,IR组最明显 ,与IP组比较差异显著 ( P <0 0 1)。⑶肝细胞AIS组未见明显调亡细胞 ,IR组和IP组AI差异有显著性 (P <0 0 1)。⑷电镜IR组超微结构破坏明显 ,IP组相对较轻 ,S组基本正常。结论 IR损伤可激活Caspase3活性 ,促进肝细胞凋亡 ,从而加重肝脏损害 ,IP可明显减轻肝脏IR损伤 ,可能的机制之一是下调Caspase3的活性来抑制肝细胞调亡。

Objective To investigate Caspase 3 activity in the ischemia reperfusion injury in rats and the protective effect of ischemic preconditioning and its possible mechanism.Methods 30 rats were randomly assigned to ischemia reperfusion (IR) group, ischemic preconditioning(IP) group,sham-operation(S)group.The serum aspartate transaminase (AST),alanine transaminase(ALT),liver caspase 3 activity,and apoptosis index(AI) of hepatocytes were examined in the three groups at 3 hours after repersusion.Results The serum AST,ALT,liver caspase 3 activity and apoptotic hepatocytes were significantly higher in both IP and IR groups than those in S group(P<0 01),and that in group IR was significantly increased compared with that in group IP(P<0 01).Electron microscope displayed that the damage of organelles in IP group was less than that in IR group as no change of organelles in groups.Conclusions IR injury may activate the apoptosis of hepatocytes by increasing Caspase 3 activity,and lead to aggravat the injury of liver.IP may reduce IR injury of liver and its possible mechanism is to inhibite apoptotic hepatocytes by down-regulating caspase 3 activity.