Effects of recombinant human erythropoietin on expression of Bid mRNA and caspase-3 activity in the brain of newborn rats subjected to cerebral hypoxia-ischemia / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of recombinant human erythropeietin(rh-EPO)on Bid mRNA and caspase-3 activity in the brain after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the possible mechanism of the neuroprotective effect of rh-EPO.Methods Ninety 7 day old male SD rats weighing 12-18 g were randomly divided into 3 groups(n=30 each)group Ⅰ sham operation(S);group Ⅱ hypoxia-ischemia group(HI)and group Ⅲ rh-EPO.The animals were anesthetized with ether.Left common carotid artery was ligated with 4-0 silk and 3 days later the animals were placed in a 2 L airtisht vessel filled with 8%O2-92%N2 at 2-3 L/min for 2 h in group Ⅱ and Ⅲ.rh-EPO 3 000 IU/kg in 4 ml/kg normal saline(NS)was administered intraperitoneally after induction of hypoxia-ischemia(HI)in group Ⅲ while in group Ⅱ NS 4 ml/kg was given IP instead.Six animals in each group were killed at 6,12,24,48 and 72 h(T1-5)respectively after IP NS or rh-EPO.Their brains were removed for determination of Bid mRNA expression(by RT-PCR)and caspase-3 activity(by colorimetric method).Results The expression of Bid mRNA was up-regulated and caspase-3 activity was significantly increased in the brain at T1-5 in HIBD group(group Ⅱ)as compared with sham operation group.rh-EPO administration significantly reduced the increase in Bid mRNA expression and caspase-3 activity in the brain induced by hypoxia-ischemia.The expression of Bid mRNA was positively correlated with the caspase-3 activity.Conclusion rh-EPO has protective effects on the brain against hypoxia and ischemia by decreasing the expression of Bid mRNA and caspase-3 activity in the brain.