Adenosine A2 A receptor antagonist SCH58261 attenuates hypoxic-ischemic brain damage in a fetal rabbit model / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM: To study the effect of adenosine A 2A receptor antagonist SCH58261 on hypoxic-ischemic brain damage ( HIBD) in a mature fetal rabbit model .METHODS:Pregnant New Zealand white rabbits at gestational day 29 were selected and were randomly divided into sham-operated group, hypoxic-ischemic group, SCH58261 0.04 mg/kg group, SCH58261 0.12 mg/kg group and DMSO group.The intrauterine rabbit HIBD model was established .All pregnant rabbits were subjected to cesarean section 24 h after the sham operation or experimental procedure to induce hypoxic-ische-mic injury in the fetus .The survival neonatal rabbits were kept in a neonatal incubator at 35℃.The general conditions of the newborn rabbits were recorded .The degree of neurobehavioral damage in the newborn rabbits was estimated by a neu -robehavioral scoring protocol .The concentration of SCH 58261 in the serum of pregnant rabbits , the serum of neonatal rab-bits and the brain tissues of neonatal rabbits was measured by mass spectrometry .The mRNA expression of Bcl-2/Bax and protein levels of p-P38 mitogen-activated protein kinase (MAPK) in the cortex, hippocampus and striatum area in the brain of the neonatal rabbits were determined by real-time PCR and Western blot .RESULTS:SCH58261 was detected in the se-rum and brain tissues of the newborn rabbits .The SCH58261 concentration was approximately 40 μg/L in the brain tissue of the newborn rabbits .The mRNA expression of Bcl-2 in the cortex , hippocampus and striatum of brain tissues in SCH58261 0.04 mg/kg group and SCH58261 0.12 mg/kg group was higher , and the mRNA expression of Bax was lower than those in HI group (P<0.05).The protein level of p-P38 MAPK in the cortex, hippocampus and striatum of brain tis-sues was reduced in SCH58261 0.04 mg/kg group and SCH58261 0.12 mg/kg group compared with HI group (P<0.05). The protein level of p-P38 MAPK in SCH58261 0.12 mg/kg group was a little lower than that in SCH 58261 0.04 mg/kg group (P<0.05).CONCLUSION: Adenosine A2A receptor antagonist SCH58261 attenuates hypoxia-ischemia induced neonatal brain injury by blocking adenosine A 2A receptor, subsequently inhibiting p-P38 MAPK phosphorylation to reduce neuronal apoptosis .