钴-原卟啉诱导大鼠血红素加氧酶-1适度过表达的研究

Optimum Overexpression of Rat Heme Oxygenase-1 Induced by CoPP

目的研究钴-原卟啉(CoPP)诱导大鼠血红素加氧酶-1(HO-1)的适度过表达,并观察其抗肝缺血/再灌注损伤(IRI)的作用。方法建立大鼠肝脏IRI模型,按体重给予不同诱导剂量的CoPP(5、2.5mg/kg及2.5mg/kg体重2次),关用锌原卟啉(ZnPP)来抑制HO-1的活性。观察血浆谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肝组织丙二醛(MDA)的变化,肝组织光镜和电镜下的改变,肝组织HO-1蛋白表达的Western印迹。结果CoPP诱导组中均有明显的HO-1蛋白表达;与缺血/再灌注(IR)组比较,CoPP诱导组动物血浆AST、LDH活性以及肝MDA含量明显降低,肝组织损伤减轻。3个剂量组中以2.5mg/kg体重诱导2次效果最佳。ZnPP的加入阻断了CoPP诱导组的这些保护作用。结论CoPP诱导HO-1适度过表达的诱导剂量为2.5mg/kg体重2次,在这一诱导剂量下HO-1过表达对肝IRI具有重要的保护作用。

Objective To study the optimum overexpression of rat heme oxygenase-1 (HO-1) induced by CoPP and its protective effect on liver ischemia/reperfusion injury (IR1). Methods Rat model of hepatic ischemia/reperfusion injury was established and the rats were given CoPP (5 mg/kg,2.5mg/kg and 2.5mg/kg body weight (twice), ip) before IR. HO-1 activity was inhibited by ZnPP. The levels of AST, LDH, MDA were measured. HO-1 protein expression was analyzed by Western blot and the pathological changes of liver were observed by light microscopy and electron microscopy. Results CoPP induction groups had significant HO-1 protein expression, and compared with IR group, the levels of AST, LDH, MDA in CoPP induction groups were decreased significantly and the liver damage was lightened. The results were best in the 2.5 mg/kg body weight (twice) group among the three CoPP induction groups. Treatment with ZnPP, an HO-1 inhibitor, abolished these beneficial effects. Conclusions The optimum induction dose of CoPP was 2.5mg/kg body weight (twice) and the overexpression of HO-1 induced by CoPP in this dose could protect rat livers from IRI.