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  

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

作　　者：张海山[1] 张学文[1] 王大民[2] 刘德全[3] 张德恒[1] 

机构地区：[1]吉林大学中日联谊医院基本外科,吉林长春130033 [2]吉林省通化市第三人民医院普通外科 [3]吉林省大安市第一人民医院普通外科

出　　处：《吉林大学学报（医学版）》2007年第4期686-689,778,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅科技发展计划项目资助课题(200505167)

摘　　要：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。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.

关 键 词：阿霉素 亚铁血红素氧化酶 再灌注损伤 缺血 肝脏 大鼠 Wistar 

分 类 号：R657.3[医药卫生—外科学] R332[医药卫生—临床医学]