OBJECTIVETo study the effect of rhIGF-1on the mRNA and protein expression of cytochrome C (Cyt-C) and caspase-3 in neonatal rats with hypoxic-ischemic brain damage (HIBD).

METHODSNinety neonatal Sprague-Dawley rats were randomly divided into three groups: normal control, HIBD, and HIBD+rhIGF-1 (rhIGF-1 was given intraperitoneally right after HI). Rat HIBD model was prepared according the Rice-Vannucci method. RT-PCR and Western blot methods were used to measure the mRNA and protein expression of Cyt-C and caspase-3 24, 48 and 72 hrs after HI (n=10 each time point).

RESULTSAt all time points, both Cyt-C mRNA and caspase-3 mRNA expression levels in the HIBD group increased compared with those in the normal control group, and those in the HIBD+rhIGF-1 group also increased compared with that in the normal control group but decreased compared with that in the HIBD group. There were statistical significances among the three groups (P<0.01). At all time points, the changes of both Cyt-C and caspase-3 protein expression in the three groups were similar to those of the mRNA expression: both Cyt-C and caspase-3 protein expression levels increased in the HIBD group compared with those in the normal control group, and those in the HIBD+rhIGF-1 group also increased compared with those in the normal control group but decreased compared with those in the HIBD group. There were statistical significances among the three groups (P<0.01).Pearson correlation analysis showed that mRNA and protein expression of Cyt-C were positively correlated to casapse-3 mRNA and protein expression in the HIBD and the HIBD+rhIGF-1 groups.

CONCLUSIONSrhIGF-1 may inhibit the Cyt-C release and caspase-3 expression, and thus provides neuroprotection against HIBD in neonatal rats.