阿霉素预处理替代缺血预处理提供鼠肝缺血耐受力的实验研究

目的 探讨缺血预处理（IPC）延迟保护作用的发生机制以及应用阿霉素预处理（DPC）是否可以模拟IPC的延迟保护作用。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10in，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HSP70和HO－1蛋白和血清TNF－α、IL－10浓度分别采用Western blot法和ELISA法测定。结果 IPC后HO－1和HSP70含量分别于12h和24h达到高峰；IPC和DPC后24h诱导HSP70、HO－1的量无显著差异（P＞0.05）。对照组缺血再灌注后3h血清中TNF－α、AST、ALT、LDH及W／D（湿重／干重）的水平明显升高，而IL－10的含量降低，和假手术组相比差异显著（P＜0.01）；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，和对照组相比差异显著（P＜0.01）。结论 IPC的延迟保护作用与HSP70和HO－1的诱导生成有关，DPC可以模拟IPC的延尺性保护作用，诱导HSP70和HO－1的产生。

Doxorubicin preconditioning instead of ischemic preconditioning in providing ischemic tolerance for rat liver

Objective To investigate the molecular mechanism of delaying protective effect of ischemic preconditioning (IPC) and determine whether doxorubicin preconditioning (DPC) can be used to replace IPC in inducing this delaying protective effect. Methods The models of sham operation and partial hepatic ischemia were established in rats. A 10 min ischemia followed by a 10 min reperfusion of the liver was inflicted in rats in IPC group while pretreatment with doxorubicin (1 mg/kg.iv.) was performed in DPC group. Normal saline was administered in the control group. The levels of liver HSP70 and HO 1 protein were determined by western blotting and the concentrations of serum TNF a and IL 10 by ELISA. Meanwhile, the activities of AST, ALT and LDH as well as liver wet to dry weight ratio (W/D) were assessed. Results The peak of HO 1 expression appeared at the 12th hour after IPC and hardly changed until the 48th hour. A strong induction of HSP70 was detected at about 24 72 hour after IPC. The levels of HO 1 and HSP70 markedly elevated at the 24th hour after IPC or DPC as compared with the control group (P<0 05), whereas no significant differences were found between IPC group and DPC group (P>0 05). An obvious increase in release of TNF a and a decrease in production of IL 10 were found in the control group at the 3rd hour after reperfusion (P<0 01), whereas the TNF a release was significantly inhibited and the IL 10 production evidently accelerated in IPC and DPC groups (P<0 01,P<0 05). At the end of reperfusion, the control group exhibited a marked increase in liver enzyme release and W/D (P<0 01). The levels of liver enzymes and W/D were significantly reduced in IPC and DPC groups (P<0 01). Conclusions Induction of HO 1 and PSP70 in delayed IPC play an critical role for the protection against hepatic ischemia/reperfusion injury. HSP70 and HO 1 were similarly induced by doxorubicin preconditioning and this preconditioning is more useful than other kinds of preconditioning in clinical practice.