Effects Of Melatonin On Free Radical And Apoptosis Of Fetal Rat Brain Suffered From Intrauterine Hypoxic-ischemic Injury

Objective To investigate the effects of melatonin(MT) on free radical and apoptosis of fetal rat brain suffered from intrauterine hypoxic-ischemic injury ,so as to explore the neuroprotective mechanisms of MT.Methods The pregnant Sprague-Dawley rats on day 19 of gestation were divided into three groups :the sham operation group(sham group),the ischemia and reperfusion group(IR group) and the melatonin group(MT group).In IR group,the utero-ovarian arteries were occluded bilaterally for 30 min in pregnant rats to induce fetal ischemia,then reperfusion were achieved by releasing the occlusion and restoring circulation for 1,6 and 24 hours.MT(10mg/kg) was injected intraperitoneally into pregnant rats 60 min pior to occlusion in MT group.A sham operation was performed in control rats.To remove the fetuses,laparotomy of the pregnant rats was performed.The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px) and the contents of malondial-dehyde(MDA) in fetal brain homogenates were determined. Meanwhile,the pathological changes of brain tissues were observed under light microscope by HE staining and TUNEL assay.Results Intrauterine ischemia and reperfusion lowered the activities of SOD ,GSH-Px and elevated the contents of MDA in fetal brain homogenates increased the number of apoptosis cells of fetal brain cortex as well as.Meanwhile,these changes in IR group increased progressively by the time of reperfusion. Treatment with MT partly reversed these changes.Conclusion Intrauterine ischemia and reperfusion produces excessive free radicals which induce fetal brain damage and increase the number of apoptosis cells of fetal brain. By the time of reperfusion,fetal brain damage increases progressively.As a powerful scavenger of free radical, MT protects fetal brain against oxidative damage and lowers the number of apoptosis cells of fetal brain.