脑室周围白质软化新生大鼠模型的创建及所伴随的白内障病变

目的：创建与人类早产儿脑室周围白质软化（periventricular leukomalacia，PVL）病理相似的可靠PVL动物模型，并探索本PVL模型所伴随的白内障病变及其形成机制。方法：新生大鼠分为PVL组和假手术对照组，通过双侧颈总动脉结扎和8％低氧下缺氧30 min，建立PVL动物模型。分别于术后1 d进行脑片TTC染色以观察脑梗死情况，术后2 d和21 d进行光镜下脑病理检查，以及术后21 d进行眼部裂隙灯检查和光镜下眼球病理检查。结果：脑片TTC染色显示PVL新生大鼠脑组织呈现大面积白色梗死区，其梗死体积达（53.45±33.90） mm3，梗死百分比为（24.98±15.44）％。光镜下病理研究证实，术后2 d的PVL新生大鼠脑室周围以及皮层下白质呈现囊性坏死和细胞凋亡，皮质神经元损伤轻微。术后21 d，其脑室周围以及皮质下白质可见多个囊性疏松坏死区域形成。相应日龄假手术组大鼠脑组织内则未观察到明显病理改变。术后21 d后，肉眼及裂隙灯下均观察到PVL组所有幼鼠双眼均呈现白内障，光镜下显示球后组织无明显病理改变。假手术组幼鼠眼部均正常。结论：通过对2日龄新生大鼠进行双侧颈总动脉结扎伴缺氧，成功创建了与人类早产儿PVL病理相似的PVL动物模型，效果肯定，重复性好。同时本建模方法也可引起白内障病变，可作为制作白内障动物模型的推荐方法之一。［中国当代儿科杂志，2007，9（3）：220-224］

Establishment of a neonatal rat model of periventricular leukomalacia and its concomitant cataract

OBJECTIVE: To establish a reliable neonatal rat model of periventricular leukomalacia (PVL) which is expected to be similar to PVL of human preterm infants pathologically, and to explore the concomitant eye lesions in the PVL model. METHODS: Two-old-day neonatal rats were randomly divided into a PVL group and a sham-operated group (n=19 each). The PVL model was established by the ligation of bilateral common carotid arteries, followed by a 30-min exposure to 8% oxygen. The cerebral infarction area was assessed with TTC staining 1 day after operation. Cerebral pathology was examined under a light micsrocope 2 and 21 days after operation. The examinations of eyes under a slip lamp and the pathology of eyeballs under a light microscope were performed 21 days after operation. RESULTS: The TTC staining cerebral slices showed there were extensive white areas of infarction in the brain of the PVL group, with an infarction area of 53.45 +/- 33.90 mm3 and a percentage of infarction of (24.98 +/- 15.44)% . Significant cystic necrosis and apoptosis around the periventricular and subcortical white matter and mild damage in cortical neurons were observed in the PVL group 2 days after operation. The more obvious cystic necrosis around the periventricular area was found in the PVL group 21 days after operation. There were no pathological changes in the brain of the sham-operated group. All of rats in the PVL group had bilateral cataracts, however, no pathological changes were observed in their postbulbar tissues. The sham-operated group did not show eye abnormal. CONCLUSIONS: The PVL animal model that was similar to PVL of human preterm infants pathologically was successfully established by the ligation of bilateral common carotid arteries, followed by 30-min hypoxia exposure, with a positive effect and a good repeatability. Cataract can also be induced by the method.