Role of heme oxygenase-1/carbon monoxide in hypoxic-ischemic brain damage in neonatal rats

Objective To observe the changes of brain heme oxygenase-1/carbon monoxide (HO-1/CO)in neonatal rats with hypoxic-ischemic brain damage(HIBD)injury and investigate the role of HO-1/CO in the recovery of HIBD. Methods Eighteen 7-day-old Wistar rats were randomly divided into sham-operated group,HIBDgroup and HIBDwith zinc protoporphyrin(ZnPP)treatment group (n=6).In the latter two groups,HIBD model was established by unilateral carotid ligation followed by timed exposure to 8%oxygen. Real-time fluorescent quantitative PCR Was performed to determine the expression of HO-1 mRNA and thiobarbituric acid(TBA)method was used to assay malondialdehyde (MDA)contentinthe braintissue of the rats.The cell apoptosis in the brain aRer HIBD was analyzed using flow cytometry,and the blood CO concentration was detected by the absorbance at 420mn and 432 nm.Results Compared to the sham-operated group.HO-1 mRNA expression and blood CO concentration were significantly increased in HIBD group and ZnPP group (P＜0.05).The rats with ZnPP group had significantly lower HO-1 mRNA expression and blood CO concentration than those in HIBD group(P＜0.05).HIBD resultedin significantly increased MDA content and cell apoptosis rate in the rat brain as compared to those in the sham-operated group(p＜0.05),and ZnPP treatment further increased the MDA content and cell apoptosis(P＜0.05). Conclusions Increased brain HO-1 mRNA expression and blood CO concentration in neonatal rats with HIBD are probably associated with the spontaneous recovery of neural tissue injury. Key words: Heine oxygenase-1; Carbon monoxide; Cerebral hypoxia; Cerebral ischemia