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目的研究褪黑素(melatonin,MT)对新生大鼠缺氧缺血性脑损伤(HIBD)的神经保护作用以及MT的用药时间窗。方法选用7日龄的SD大鼠,随机分为假手术组、模型组(HIBD组)、MT治疗组(按给药时间分为HIBD前组、0h组、1h组和2h组),即治疗组在各不同时间给予腹腔注射1次MT10mg/kg,各组动物分别在术后6h、12h、24h、48h、72h处死。用酶联免疫吸附法检测血清中神经元特异性烯醇化酶(NSE)的水平,用免疫组化法检测脑组织NSE的表达变化。结果HIBD模型组血清NSE水平显著高于MT各治疗组(P<0.01),HIBD模型组皮质NSE阳性细胞数显著低于MT各治疗组(P<0.01或P<0.05);MT治疗组各组间比较,HIBD前组、0h组、1h组血清NSE和皮质NSE阳性细胞数的变化差异性不明显(P>0.05),但它们与后2h组在血清NSE和皮质NSE阳性细胞数的变化上有显著性差异(P<0.05);脑组织中NSE的变化与血清中NSE的变化显著负相关(r=-0.92)。结论褪黑素对新生大鼠缺氧缺血性脑损伤有预防和治疗作用,能有效地保护NSE的活性。褪黑素在HIBD的治疗上存在时间窗,预防用药和HIBD后2h内给药效果明显,而且HIBD后1h内给药优于HIBD后2h给药。
Objective To study the neuroprotective effects of melatonin (MT) on hypoxic-ischemic brain damage (HIBD) in neonatal rats and the time course of MT. Methods 7-day-old SD rats were randomly divided into sham operation group, model group (HIBD group) and MT treatment group (divided into pre-HIBD group, 0h group, 1h group and 2h group according to the administration time) Groups were given intraperitoneal injection of MT10mg / kg at different times, and the animals in each group were sacrificed at 6h, 12h, 24h, 48h and 72h respectively. Serum levels of neuron specific enolase (NSE) were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of NSE in brain tissues was detected by immunohistochemistry. Results The serum levels of NSE in HIBD model group were significantly higher than those in MT treatment group (P <0.01). The number of cortical NSE positive cells in HIBD model group was significantly lower than that in MT treatment group (P <0.01 or P <0.05) There was no significant difference in the number of NSE positive cells and NSE positive cells in HIBD, 0h and 1h groups (P> 0.05), but there was no significant difference between them in the changes of serum NSE and cortical NSE positive cells (P <0.05). The change of NSE in brain tissue was negatively correlated with the change of NSE in serum (r = -0.92). Conclusion Melatonin can prevent and treat hypoxic-ischemic brain damage in neonatal rats and can effectively protect the activity of NSE. Melatonin in the treatment of HIBD there is a time window, prophylaxis and administration within 2h after HIBD obvious effect, and within 1h after HIBD administration superior to HIBD after 2h administration.