关键词: 亚铁血红素氧化酶, 再灌注损伤, 缺血, 肝脏, 大鼠, Wistar

Abstract: To investigate the protective effect of heme oxygenase-1 (HO-1) induced by doxorubicin on hepatic ischemia-reperfusion in rats and its mechanism. Methods Fourty eight male Wistar rats were divided randomly into six groups (eight rats in each group)：normal group(N)，doxorubicin group(DOX)，ZnPP group，ischemia reperfusion group(IR)，DOX +IR group(DOX-IR) and DOX +ZnPP+IR group.The contents of serum alanine aminotransferase(ALT)，aspartate aminotransferase(AST) and lactate dehydrogenase(LDH) were examined as liver function indicators.Serum endothelin（ET）and tumor necrosis factor-α（TNF-α） were also measured as markers of stress.HO-1 protein expression was measured respectively by Western blotting and immunohistochemical method (S-P).Ultrastructural changes were investigated by transmission electron microscope. Results The values of ALT，AST，ET-1, and TNF-α in DOX -IR group were significantly lower than those in IR group (P<0.05)，but there was no significant difference between DOX group and normal group (P>0.05).There was no significant difference in liver function test between DOX -ZnPP-IR group and IR group (P>0.05).The results of Western blotting and immunohistochemical method showed that HO-1 protein expression increased in DOX group and DOX -IR group，and was negative in normal group.More distruction of ultrastructural changes of hepatic cells in IR group was found than in DOX-IR group by transmission electron microscope. Conclusion Doxorubicin pretreatment could protect the liver from ischemia-reperfusion injury，which may be related to HO-1 expression induced by doxorubicin,low dosage of doxorubicin does little harm to rat liver.

Key words: heme oxygenase, reperfusion injury, ischemia, liver, rats, Wistar