未成熟大鼠脑白质损伤中巨噬细胞和小胶质细胞的变化及别嘌呤醇的影响

Changes of macrophages and microglias in white matter damage and effects of allopurinol in premature rats

目的通过制作早产儿脑白质损伤动物模型,探讨巨噬细胞和小胶质细胞在早产儿脑白质损伤中的变化及别嘌呤醇(allopurinol,ALLO)的影响。方法将新生1日龄SD大鼠42只随机分为假手术组(Sham,n=14)、双侧颈总动脉结扎组(BCAO,n=14)及ALLO干预组(n=14),行BCAO制作脑白质损伤模型。观察BCAO后7 d(P7,每组各6只)和14 d(P14,每组各8只)脑组织病理改变及巨噬细胞和小胶质细胞免疫组化变化。结果BCAO组白质改变明显,ALLO组较之明显减轻;P14的ALLO组较[(2.44±0.71)%]BCAO组[(3.27±0.73)%]平均脑室大小指数明显减小(P<0.05)。各组动物脑胼胝体、海马繖及内囊部位均有ED1染色阳性细胞出现,但BCAO组染色阳性细胞数明显多于其他两组,且染色增强。结论利用出生1日龄新生大鼠行BCAO可成功制备早产儿脑白质损伤动物模型。巨噬细胞和小胶质细胞的活化在早产儿脑白质损伤中可能发挥了重要作用。ALLO对缺血引起的早产大鼠脑白质损伤具有一定的保护作用。

Objective The aim of this study was designed to investigate the changes of macrophages and activated microglias in white matter damage（WMD） in premature infants and effects of allopurinol. Methods An animal model for WMD was established by bilateral carotid artery occulation（BCAO）.Forty-two newborn SD rats（1 day old） were divided randomly into 3 groups： sham surgery group（Sham）,BCAO group（BCAO） and allopurinol treated group（ALLO）.Pathological changes were studied 7 days and 14 days after BCAO,respectively.Macrophages and activated microglias were detected by immunohistochemistry 7 days and 14 days after BCAO,respectively. Results In BCAO group,Ten cases had mild or severe rarefaction in the corpus callosum area,especially at the cingulum.Pathological changes of white matter were found in 4 cases in internal capsule.Eight cases had subcortex white matter rarefaction.The extent of white matter rarefaction in ALLO group was reduced significantly.Enlargement of bilateral ventricles was found in 6 of 8 cases in BCAO group.Compared to BCAD group [（3.27±0.73）%] the average ventricle size was reduced significantly in ALLO group [（2.44±0.71）%]（P〈0.05）.ED1 positive cells were found in corpus callosum,hippocampus,and internal capsule in all groups.BCAO group had more ED1 positive cells than the other two groups,and the staining extent in BCAO group was stronger than that in the other two groups. Conclusions BCAO could be used in newborn rats（1 day old） to establish a premature WMD animal model.Macrophages and microglias may play an important role in premature WMD.ALLO may have a potential protective effect on premature SD rat with ischemic WMD.