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Objectives: Our study intended to investigate which isoenzyme (HO-1 or HO-2) might be target to protect neurons in rat brains against hypoperfusion and its putative mechanism.Methods: 60 adult male SD rats were randomly divided into sham-operated group and model group. Model group rats were performed by permanent bilateral common carotid arteries occlusion(2 vessel occlusion,2VO), then randomly divided into 5 groups (1 day after 2VO, 7 days after 2VO, 14 days after 2VO, 21 days after 2VO and 28 days after 2VO). While sham-operated group animals were separated bilateral common carotid arteries without ligation. Brain blood, HO-1 concentration, the expression of HO-1, HO-2, heme, ferritin, Cyto C and ATP synthase, the activity of HO and COX were detected at different time points.Results: We discovered that blood flow was immediately reduced at 1 day after 2VO (P<0.001), and did not return to the baseline at 28 days. HO-1 mRNA and protein expression were increased statistically, and reached to the peak at 7 days in hippocampus (P<0.01) and at 14 days in cortex (P<0.01), accompanied by a parallel HO activity. While the upregulation of HO-1 concentration had not statistically difference at all time points. However, the expression of HO-2 mRNA and protein were just reverse. In addition, the upregulation of HO-1 caused decrease of heme protein, then the latter resulted in ferritin increase and the reduction of Cyto C and ATP synthase protein expression, which were synthesized depending on heme availability. And mitochondrial COX activity was decreased in model groups, and reached to the bottom at 14 days after 2VO in hippocampus and cortex (P<0.001).Conclusion: In conclusion, our findings demonstrated that the upregulation of HO-1 was accounted for HO activity in rats’brain after chronic cerebral hypoperfusion. It suggested that HO-1 might have important biological roles in regulating heme protein turnover and protecting against hypoperfusion by increasing ferritin and decreasing mitochondrial respiratory activities.
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