促红细胞生成素在新生大鼠缺氧缺血性脑损伤中的作用及其机理研究-儿科学专业论文.docxVIP

Backgrounds and aims Abstract Hypoxic–ischemic brain damage can result from perinatal asphyxia and is an important cause of neonatal mortality and subsequent sequelae. Due to the complicated pathogenesis, the associated clinical therapeutics is always disputable. EPO is a hematopoietic cytokine which has recently been found in the nervous system，recent studies suggest that EPO has neuroprotective effects. The aim of this study was to investigate the pathological change of hypoxic–ischemic neonatal brain in rats and evaluate whether EPO treatment, as a novel approach, would reduce the brain damage against hypoxic–ischemic damage. Methods ⑴7-day-old Sprague-Dawley rats were randomly divided into 3 groups: sham-operated group, HIBD group and HIBD+EPO group. The last two groups underwent left carotid artery ligation followed by hypoxia (8% O2) for 2h on day 7 and giving either vehicle or EPO (1000 U/kg i.p. qd×3).⑵Water content of the brain, changes of brain histopathology, and bcl-2 protein expression in the cortex and hippocampi were observed 3 days after hypoxia-ischemia.⑶At 6h、 24h 、 72h 、 120h after hypoxia-ischemia, Intracellular free Ca2+ was measured by fluorospectrophotometry with fluorescent indicator Fura-2/AM; the malondialdehyde (MDA)， the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were tested.⑷Long-term behavioral outcomes was assessed by Morris water-maze(place navigation test and spatial probe test )after 4 weeks, rats were killed 6 days later, the extent of atrophy of the hypoxic-ischemic hemisphere and changes of brain histopathology were observed. Results Representative brain edema, pathological lesions early 3 days after hypoxic–ischemic by specimen weight and histological section, suggest the HIBD model was successfully prepared. Erythropoietin treatment significantly mitigated brain edema, pathological lesions early 3 days after hypoxic–ischemic. 3 days after hypoxic–ischemic, the expression of bcl-2 protein in cor