阿霉素诱导亚铁血红素氧化酶-1对大鼠肝脏缺血再灌注的保护作用

目的:探讨阿霉素诱导亚铁血红素氧化酶-1(HO-1)对大鼠肝脏缺血再灌注的保护作用及其机制。 方法:48只雄性Wistar大鼠，随机分成6组（每组8只）：正常组(N)、阿霉素组(DOX)、原卟啉锌-Ⅸ组(ZnPP)、缺血再灌注组(IR)、阿霉素+缺血再灌注组(DOX-IR)和阿霉素+原卟啉锌+缺血再灌注组(DOX-ZnPP-IR)。测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及乳酸脱氢酶(LDH)含量作为肝功能指标；放射免疫法测定血清肿瘤坏死因子(TNF-α)和内皮素(ET)作为应激标志物指标；应用Western blotting法和免疫组织化学S-P法观察HO-1蛋白表达；透射电子显微镜观察细胞超微结构变化。 结果:DOX-IR组ALT、AST、ET-1和TNF-α值均显著低于IR组 (P<0.05)；DOX组与正常组比较，肝功能、ET-1和TNF-α值差异无显著性 (P>0.05)；DOX-ZnPP-IR组与IR组比较，肝功能值差异无显著性(P>0.05)。Western blotting法和免疫组织化学S-P法检测显示DOX 组和DOX-IR组 HO-1蛋白表达增加，HO-1在正常肝脏内的表达呈阴性。透射电镜检查IR组肝细胞细可见明显的细胞器损害现象，DOX -IR细胞器受损较轻。 结论：阿霉素预处理可以提高器官对缺血再灌注损伤的耐受性，其机制可能与阿霉素所诱导的HO-1表达有关，小剂量阿霉素对大鼠肝脏未造成明显损害。

Protective effect of heme oxygenase-1 induced by doxorubicin on hepatic ischemia-reperfusion in rats

Objective 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.