The Effects Of Melatonin On Oxidative Damage And Apoptosis Of Fetal Brains Induced By Intrauterine Infection

Objective : To establish the intrauterine infection models of rats and investigate the effects of melatonin(MT) on oxidative damage of fetal brains induced by intrauterine infection, so as to study the protective effects of MT.Methods: The 72 d19 of pregnant Sprague-Dawley rats were divided randomly into three groups:the blank control group, the intrauterine infection group (LPS group) and the melatonin group (MT group), 24 in each group. To establish models, fetal rat brain damage made by lipopolysaccharide (LPS)-induced intrauterine infection. In LPS group, the pregnant rats received an intraperitoneal (i.p.) injection of LPS (500μg/kg). In MT group, the rats were treated with LPS 500μg/kg and MT 10 mg/kg simultaneously. Then, according the time after injection, the pregnant rats were divided into six groups (n=4) respectively: 1h,6h,12h,24h,48h,72h. To remove the fetuses, laparotomy of the pregnant rats was performed. The activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) in fetal brain homogenates were detected. Meanwhile, the pathological changes of placenta and brain tissues were observed under light microscope by HE staining, in addition, the number of apoptotic brain cells were counted through in situ labeling method (TUNEL).Results:1. The intrauterine infection models of rat were constructed successfully; there were histopathological inflammation changes in placenta tissues which were observed under light microscope by HE staining in the intrauterine infection group.2. Intrauterine infection lowered the activities of SOD and elevated the contents of MDA in fetal brain homogenates. Meanwhile, these changes in intrauterine infection group increased progressively by the time of infection (P <0.05).3. MT had improved the SOD activities and lowered the MDA contents of fetal brain tissues, meanwhile, reduced the number of apoptotic cells of fetal brains (P <0.05). Conclusions:1. Successfully established by intraperitoneal injection lipopolysaccharide-induced intrauterine infection of fetal rat brain injury models, which demonstrated that intrauterine infection was an important factor in fetal brain injury.2. There was lipid peroxidation, more apoptotic brain cells in fetal rat brains due to intrauterine infection, by the time of infection, fetal brain damage increased progressively.3. MT had antagonistic effects on oxidative damage of fetal brain, and also inhibited intrauterine infection-induced apoptosis of brain cells, which indicating that MT protested the fetal brain damage suffered from intrauterine infection.