Balduini W, Carloni S, Perrone S, Bertrando S, Tataranno M L, Negro S, Proietti F, Longini M, Buonocore G
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
J Matern Fetal Neonatal Med. 2012 Apr;25 Suppl 1:119-24. doi: 10.3109/14767058.2012.663232. Epub 2012 Mar 5.
Oxidative stress (OS) plays a key role in perinatal brain damage. The aim of this study is to evaluate the effectiveness of melatonin as a neuroprotective drug by investigating the influence of melatonin on OS and inflammation biomarkers in an animal model of cerebral hypoxia-ischemia.
Five minutes after hypoxic-ischemic (HI) injury melatonin was administered to 28 rats (HI-Mel group). At the same time, 28 hypoxic-ischemic rats were vehicle-treated (V-HI group). Five rats were used as sham operated controls (CTL). OS biomarkers: isoprostanes (IsoPs), neuroprostanes (NPs) and neurofurans (NFs), and microglial activation markers (glial fibrillary acidic protein [GFAP] and monoclonal antirat CD68 [ED1]) were measured in the cerebral cortex of the two lobes.
A significant increase of IsoPs on the left lobe was observed in V-HI after 1 hour (h) from HI injury (p < 0.001); a significant increase of NPs on both side (p < 0.05) and a significant increase of NFs on the left (p < 0.05) were also observed in V-HI after 24 h. A significant increase of IsoPs on the left (p < 0.05) and of NPs on both lobes (p < 0.05) were observed in HI-Mel after 48 h. The ED1 and GFAP expression was lower in the HI-Mel brain tissue.
Melatonin reduces OS and inflammatory cells recruitment and glial cells activation in cerebral cortex after neonatal HI damage. These results lay the groundwork for future clinical studies in infants.
氧化应激（OS）在围产期脑损伤中起关键作用。本研究的目的是通过研究褪黑素对脑缺氧缺血动物模型中OS和炎症生物标志物的影响，评估褪黑素作为一种神经保护药物的有效性。
在缺氧缺血（HI）损伤后5分钟，对28只大鼠给予褪黑素（HI-Mel组）。同时，对28只缺氧缺血大鼠进行载体处理（V-HI组）。5只大鼠作为假手术对照（CTL）。在两个脑叶的大脑皮层中测量OS生物标志物：异前列腺素（IsoPs）、神经前列腺素（NPs）和神经呋喃（NFs），以及小胶质细胞激活标志物（胶质纤维酸性蛋白[GFAP]和抗大鼠单克隆CD6（ED1））。
在HI损伤后1小时，V-HI组左叶IsoPs显著增加（p<0.001）；在24小时后，V-HI组两侧NPs显著增加（p<0.05），左叶NFs显著增加（p<0.05）。在48小时后，HI-Mel组左叶IsoPs显著增加（p<0.05），两叶NPs显著增加（p<0.05）。HI-Mel脑组织中ED1和GFAP表达较低。
褪黑素可减少新生儿HI损伤后脑皮层中的OS以及炎症细胞募集和胶质细胞激活。这些结果为未来对婴儿的临床研究奠定了基础。
