Involvement of heme oxygenase-1 in delayed cardioprotection induced by monophosphoryl lipid A in rats.
Abstract
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.
Keywords:
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.