缺血后处理对大鼠缺血再灌注损伤肝脏血红素加氧酶-1表达的影响

Effects of ischemic postconditioning on the expression of heme oxygenase-1 in the liver graft with ischemia and reperfusion injury in rats

目的探讨缺血后处理对大鼠缺血再灌注损伤肝脏血红素加氧酶-1（HO-1）表达的影响。方法将56只健康雄性sD大鼠随机分为4组：假手术组（Sham组）（n=8）、缺血再灌注组（I／R组）（n=16）、缺血后处理组（IPO组）（n=16）和HO抑制剂锌原卟啉组（ZnPP组）（n=16）。供肝取出后均置于0～4℃生理盐水中，冷保存时问90rain，受鼠无肝期控制在15min以内。各组于术后6h分别留取血液及肝组织。测定血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的活性、肝组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、HO-1mRNA的含量以及组织病理学检查。结果与Sham组比较，I／R组缺血肝组织中MDA含量增加，SOD活性降低（P〈0．05），I／R组HO-1表达明显升高（P〈0．05）。与I／R组比较，IPO组缺血肝组织中MDA降低，SOD活性升高（P〈0．05），HO—1表达显著增强（P〈0．05）。与IPO组比较，ZnPP组MDA含量升高，SOD活性降低（P〈0．05），HO-1表达明显减少（P〈0．05）。组织病理学检查亦证实上述结果。结论缺血后处理能明显减轻大鼠移植肝脏缺血再灌注损伤，其机制可能与增加HO-1的表达和增强移植肝脏抗氧化能力有关。

Objective To investigate the effects of ischemic postconditioning on the expression of HO-1 in the liver graft ischemia and reperfusion injury in rats. Methods Fifty-six male SD rats were randomly divided into four groups ： sham-operation group（sham） （ n = 8 ）, ischemia and reperfusion group（ I/ R） （ n = 16） ,ischemie postconditioning group（IPo） （ n = 16） and inhibitor of HO-1 group（ZnPP） （ n = 16）. Donor livers were preserved in 0-4℃ normal saline, and the period of cold preservation and anhepatie phase were 90 rain and 15 min. At 6 h after portal vein reperfusion, blood samples were obtained from the abdominal aorta to determine the level of serum alanine aminotransferase （ALT） , aspartate aminotransferase （AST） , simultaneously liver tissues were taken to determine the level of malondialdehyde （ MDA ）, superoxide dismutase（ SOD） and heme oxygenase-1 （HO-1）mRNA. The changes of liver tissues were observed by HE staining and electronmicroscope. Results SOD activity was significantly lower whereas MDA content was significantly higher in I/R group than that in Sham group （P 〈0. 05）. The expression of HO-1 in I/R group was higher than that in Sham group （ P 〈 0. 05 ）. MDA content was significantly lower whereas SOD activity was significantly higher in IPO group than that in I/R group（P 〈0. 05） ,and the expression of HO-1 in IPO group was significantly stronger than that in I/R group（ P 〈0. 05 ）. SOD activity and the expression of HO-1 were significantly lower whereas MDA content was significantly higher in ZnPP group than that in I/R group （P 〈 0. 05 ）. The changes of liver tissues also proved the previous results. Conclusions Ischemic postconditioning attenuates liver graft injury induced by I/R in rats. The mechanism might be related with the induction of HO-1 and enhancement of liver graft antioxidation.