血红素氧合酶—1介导单磷酰酯A诱导的心脏延迟保护

目的:研究血红素氧合酶-Ⅰ(HO-Ⅰ)是否参与单磷酰酯A诱导的心脏延迟保护作用.方法:在体大鼠心脏缺血-再灌损伤模型,缺血前24小时应用单磷酰酯A(500μg/kg,ip)诱导心脏延迟保护,观察单磷酰酯A对心肌梗死面积、肌酸激酶(CK)活性以及血清一氧化氮(NO)浓度的影响,并检测心脏HO-ⅠmRNA和蛋白的表达.结果:单磷酰酯A明显缩小心梗面积,减少CK释放以及显著升高血清NO浓度(P<0.01).这些作用可被预先给予一氧化氮合酶抑制剂L-亚硝基精氨酸甲酯(L-NAME,10mg/kg,ip)和血红素氧合酶抑制剂锌原叶啉LX(ZnPP-9,45μmol/kg,ip)所取消(P<0.01);单磷酰酯A明显增加心脏HO-ⅠmRNA和蛋白的表达,这一作用不被L-NAME所影响(P>0.05).结论:HO-Ⅰ/NO途径介导单磷酰酯A诱导的延迟心脏保护.

Involvement of heme oxygenase-1 in delayed cardioprotection induced by monophosphoryl lipid A in rats

AIM: To explore whether the heme oxygenase-1 (HO-1) pathway is involved in the delayed cardioprotection induced by monophosphoryl lipid A (MLA). METHODS: Sprague-Dawley rats were pretreated with MLA 24 h before the experiment. Ischemia-reperfusion injury was induced by 60 min coronary artery occlusion followed by 3 h reperfusion. Infarct size, the serum creatine kinase (CK) activity, the serum content of nitric oxide (NO), and expression of HO-1 mRNA and protein in the heart were measured. RESULTS: Pretreatment with MLA (500 microg/kg, ip) markedly reduced infarct size and CK release and increased the serum content of NO (P < 0.01). The effects of MLA were completely abolished by pretreatment with L-nitroarginine methyl ester (L-NAME 10 mg/kg, ip), an inhibitor of NO synthase (P < 0.01), or Zinc protoporphyrin IX (45 micromol/kg, ip), an inhibitor of HO (P < 0.01). MLA caused a significant increase in the expression of HO-1 mRNA and protein, an effect which was not affected by L-NAME (P > 0.05). CONCLUSION: The results suggest that the HO-1/NO pathway is involved in the delayed cardioprotection induced by MLA.