Abstract: To establish a simple and stable rat model of full-term infants with the whole
hypoxic-ischemic brain damage (HIBD) in full-term infants and to explore the evaluation method of the
model. Method Eighty-two 10-day-old SD rats were randomly divided into sham operation group
( Sham, n = 22) and model group (HIBD, n = 60) . The whole brain HIBD rat model of full-term infants
was prepared by ligating the bilateral common carotid arteries of 10-day-old SD rats for 1. 5 hours and
revascularization after 30 minutes of hypoxia. The sham operation group did not receive ischemia and
hypoxia treatment. ( 1) Pathological related detection: 3 days after operation, TTC staining, HE and
Nissl staining, hippocampal electron microscopy were used to observe the pathological changes of brain
tissue. Brain water content was measured by brain dry-wet ratio method to evaluate brain edema. ( 2)
Behavioral evaluation: Convulsion assessment was performed 12 hours after surgery, Longa score was
performed 3 days after surgery, suspension test was performed 10 days after surgery, and Morris water maze test was performed 3 weeks after surgery. HIBD was graded according to the postoperative general
condition and behavioral experiment result. Result Compared with the sham operation group, TTC
staining showed bilateral white infarcts in the HIBD group. HE and Nissl staining showed disordered
arrangement and necrosis of neurons in hippocampus. Electron microscopy showed neuronal cell edema,
mitochondrial vacuolization, and increased autophagic lysosomes in the hippocampus. Brain water content
increased significantly (P<0. 01) . Compared with the sham operation group, rats in the HIBD group had
seizures with different degrees of motor nerve dysfunction in the early stage, and developmental delay and
decreased learning and cognitive ability in the long term ( P < 0. 01 ) . Conclusion The pathological
model of moderate to severe neonatal rat HIBD can be reproduced by ligation of bilateral common carotid
arteries, hypoxia and recanalization in 10-day-old neonatal rats.

Key words: hypoxic-ischemic encephalopathy, animal model, rat

摘要： 目的 建立一种简单稳定、适宜临床研究的足月儿全脑缺氧缺血性脑病( HIBD) 大鼠模型并探讨该模型的评
价方法。 方法 将 10 日龄 SD 大鼠 82 只,随机分为假手术组( Sham,n = 22)和模型组( HIBD,n = 60) 。 通过结扎 10
日龄 SD 大鼠双侧颈总动脉,缺血 1. 5 h,缺氧 30 min 后给予血管再通的方法,制备足月儿全脑 HIBD 大鼠模型;假
手术组不做缺血和缺氧处理。 (1)病理相关检测:术后 3 d,进行 TTC 染色、HE 与尼氏染色,海马区电镜检测,观察
脑组织病理结构变化;脑干湿比重法测脑含水量评估脑水肿情况。 (2)行为学评价:术后 12 h 进行惊厥评估,术后
3 d 进行 Longa 评分,术后 10 d 进行悬吊实验,术后 3 周进行 Morris 水迷宫实验。 结合术后一般情况与行为学实验
结果进行 HIBD 分级。 结果 与假手术组相比,HIBD 组 TTC 切片染色可见双侧白色梗死灶;HE 与尼氏染色可见
海马区神经元排列紊乱、坏死脱失;电镜检测可见海马区神经元细胞水肿,线粒体空泡化,自噬溶酶体增多;脑含水
量显著升高(P<0. 01) 。 与假手术组相比,HIBD 组大鼠早期可有惊厥发作伴不同程度运动神经功能障碍,远期可
出现发育迟缓、学习认知能力降低(P<0. 01) 。 结论 结扎 10 日龄大鼠双侧颈总动脉,缺氧后再通,能较稳定地复
制出中重度足月儿全脑 HIBD 大鼠模型,可为进一步探索 HIBD 发病机制与治疗用药提供理想的动物模型。

关键词: 缺氧缺血性脑病, 动物模型, 大鼠