HSP-70和HO-1诱导对鼠肝缺血再灌注损伤的保护作用  

Protective effects of induction of heat shock protein 70 and heme oxygenase-1 on ischemia/reperfusion injury of rat livers

作　　者：吴刚[1] 梁健[1] 成东华[1] 赵宁[1] 刘永锋[1] 

机构地区：[1]中国医科大学附属第一医院外科,辽宁沈阳110001

出　　处：《中国医科大学学报》2004年第2期125-127,共3页Journal of China Medical University

摘　　要：目的 :探讨缺血预处理 (IPC)和阿霉素预处理 (DPC)延迟保护作用的发生机制。方法 :建立大鼠部分肝脏热缺血再灌注模型。IPC组采用肝脏缺血 10min ,再灌注 10min ,DPC组经静脉注射阿霉素 (1mg/kg体重 ) ,对照组等量生理盐水注射。肝组织热休克蛋白 70 (HSP 70 )、血红素氧化酶 1(HO 1)蛋白、血清肿瘤坏死因子α(TNF α)、白细胞介素 10 (IL 10 )浓度分别采用Westernblot法和ELISA法测定。结果 :IPC后HO 1和HSP 70含量分别于 12h和 2 4h达到高峰 ;IPC和DPC后 2 4h诱导HSP 70、HO 1的量无显著差异 (P >0 .0 5 )。对照组缺血再灌注后 3h血清中TNF α、天冬氨酸转氨酶 (AST)、谷丙转氨酶 (ALT)、乳酸脱氢酶 (LDH)及湿重 /干重 (W /D)的水平明显升高 ,而IL 10的含量降低 ,与假手术组相比差异显著 (P <0 .0 1) ;IPC或DPC后降低了TNF α的释放和AST、ALT、LDH及W /D的水平 ,提高了IL 10的含量 ,与对照组相比差异显著 (P <0 .0 1)。结论 :IPC和DPC的延迟保护作用与HSP 70和HO 1的诱导生成有关。Objective: To investigate the molecular mechanisms of delayed ischemic preconditioning(IPC) and doxorubicin preconditioning(DPC) to induce ischemic tolerance. Methods: The models of sham-operation and partial hepatic ischemia were established in rats. The IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Animals in the DPC group were pretreated with doxorubicin(1 mg/kg, iv). The control rats received saline. The expressions of heat shock protein 70 (HSP-70) and heme oxygenase-1( HO-1) protein in liver were examined with Western blotting.The concentrations of serum tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) were determined by using ELISA and the activities of serum aspartate transaminase(AST),alanine transaminase( ALT), and lactate dehydrogenase(LDH), and ratio of wet to dry weight of livers (W/D) were assessed. Results:The expression of HO-1 reached peak 12 hours after IPC, and hardly changed until 48 hours. A strong induction of HSP-70 was detected about 24 to 72 hours after IPC. The levels of HO-1 and HSP-70 obviously elevated24hoursafterIPC or DPC compared with the control (P<0.05), whereas no significant difference was foundbetweenIPCgroupandDPCgroup (P>0.05). Level of TNF-α increased and that of IL-10 decreased in the control group 3 hours after reperfusion(P<0.01), whereas level of TNF-α decreased and that of IL-10 increased in the IPC and DPC groups (P<0.01). In the control group, level of liver enzyme and W/D increased at the end of reperfusion(P<0.01). The levels of liver enzymes and W/D were significantly reduced in the IPC and DPC groups(P<0.01). Conclusion: The delayed protective effects of IPC and DPC are closely related to the induction of HSP-70 and HO-1.

关 键 词：缺血预处理 再灌注损伤 热休克蛋白70 血红素氧化酶1 

分 类 号：R657.3[医药卫生—外科学]