Effect Of Heme Oxygenase-2 On Hemoglobin Toxicity After ICH

Background : Hemoglobin accumulates in intracranial hematomas and is a potent oxidant. Growing evidence suggests that it contributes to delayed injury to surrounding tissue, and that this process is affected by the heme oxygenase enzymes. Much controversy exists regarding the predomant effect of HO in the setting of oxidative injury, and this controversy is rooted in the further biochemistry of heme breakdown products. HO may have a pro-oxidant effect, as the iron released from heme. By producing biliverdin and its metabolite bilirubin, however, HO may act with an antioxidant effect, because bilirubin is a potent antioxidant.Aim: To investigate the effect of heme oxygenase-2 on hemoglobin toxity after ICH. And using an adenoviral vector encoding the antisense human HO-2 gene to specifically decreaseHO-2 expression in neurons and protect the neurons from hemoglobin toxity.Method: Stereotactic injection of Hb into the striata of the WT and HO-2 knockout to mimic the ICH. Protein oxidation was detected by an assay for carbonyl groups. Striatal lipid peroxidation detected by the malondialdehyde assay and striatal cell viability determed by the MTT assay. According to the results, an adenoviral vector encoding the antisense human HO-2 gene was developed and injected into the striatum after Hb injection. Neuron counts, protein oxidation and lipid peroxidation were determed at 5d after virus injection.Result: In HO-2 knockout mice, the protein oxidation of the striata with the Hb injection was significantly lower than that of the WT mice. Similarly, striatal lipid peroxidation was significantly greater in the Hb-injected striata of wild-type mice than in HO-2 knockout mice. Striatal cell viability of striata in HO-2 knockout was significantly greater than that of the WT mice at 72 h. The adenoviral vector encoding the antisense human HO-2 gene was developed successfully and specifically decreased the HO-2 expression in neurons. Neuronal viability of the mice with the virus injection was significantly greater than that of the control mice.the protein oxidation and lipid peroxidation of the with the virus injection were significantly lower than that of the control mice.Conclusion: These results support the hypothesis that HO-2...