3-硝基丙酸脑内注射诱导新生鼠脑室周围脑白质软化模型的建立

目的探讨脑内注射3-硝基丙酸（3-NPA）建立新生鼠脑室周围白质软化（PVL）模型的可行性，探索可靠的造模方法。方法新生5d（P5）SD大鼠64只，随机分成NPA与磷酸盐缓冲液（PBS）组，每组32只，脑立体定位仪定位于左侧脑室上方胼胝体，分别注入3-NPA（300mmol／L）和等量PBS，于造模后24h（P6）、48h（P7）、72h（P8）、9d（P14）灌注固定取脑，作HE染色及少突胶质细胞04、髓鞘碱性蛋白（MBP）免疫组织化学染色。结果HE染色显示P6、P7、P8NPA组皮质下及脑室周围白质出现疏松及液化灶，P14出现脑室扩大，脑室指数较PBS组高，有显著性差异（P〈0．01），脑皮质无明显变化；04染色示NPA组阳性细胞较PBS组明显减少，差异有显著性（P〈0．01）；MBP免疫染色示NPA组平均光密度值较PBS组低，有显著性差异（P〈0．05）。结论3-NPA脑内注射诱导新生鼠PVL模型以脑室周围白质损伤为突出表现，皮质无明显改变，可作为疾病研究的可靠模型。

Model for Periventricular Leukomalacia of Neonatal Rat Induced by Intracerebral Injection of 3-Nitropropionic Acid

Objective To explore the feasibility on establishing the model for periventricular leukomalacia (PVL) by intracerebral injection of 3-nitropropionic acid (3-NPA) and realistic model for concerned studies.Methods Sixty-four SD rat pups of both sexes at the age of postnatal day 5 (P5) were divided into 2 groups: NPA group (n=32) and phosphate buffered solution (PBS) group (n=32), and injected the same volume of 3-NPA and PBS with a tip located at the corpus callosum above the left ventricle by stereotaxis instrument, respectively.Twenty-four hours(P6),48 h(P7),72 h(P8) and 9 d(P14) after injection, the injections were transcardially perfused and then brains were collected. Then ice sections of brains were performed HE staining and oligodendrocyte O4 and myelin basic protein (MBP) immunostai-ning.Results HE staining showed that, in NPA group, sub-cortical and periventricular white matter rarefaction were observed on P6, P7 and P8, significant lateral ventricle enlargement was found on P14 and the ventricle size index was significantly higher compared to PBS group (P<0.01), and no histological changes in gray matter were noted. O4 staining showed positive cells in NPA group decreased apparently compared to PBS group (P<0.01). MBP immunostaining showed the mean optical density value in NPA group was significantly lower than that in PBS group (P<0.05).Conclusions The model for PVL induced by intracerebral injection of 3-NPA is characterized by damage to the periventricular white matter left the cortical grey matter largely intact. The model can be used to study concerned disease as a realistic one.