Abstract: Objective　The pathological changes in brain tissue during the acute phase were analyzed by establishing a neonatal SD rat HIE model.Methods　CT imaging data of 54 newborns with severe HIE in our hospital were collected to analyze the location of brain injury. The HIE animal models of 24 newborn 7-day-old SD rats were established, and their brain tissues were collected at 1, 3, 6, and 9 hours after modeling. Ischemic area and pathology of thalamus, cortex, and hippocampal tissue, and changes of  cellular oxidative stress, apoptosis and necrosis were analyzed through TTC, HE, Nissl staining, and flow cytometry.Results　The thalamus of children with severe HIE were most affected. The morphology of neurons in the right thalamus LDDM, LDVL, cortex S1BF, M2, RSA, and hippocampus CA1 regions had changed, and the staining had gradually become lighter and the number of cells had gradually decreased after 1-3 hours of modeling. During 3-6 h, the staining in each region had become lighter and lighter, and the changes of cell morphology and quantity were significant. At the same time, ischemic necrosis of cortical S1BF region had gradually appeared. During 6-9 h, The changes in tissue morphology and cell numbers of each regions were more pronounced, and ROS began to increase. Conclusion　3-6 hours after the establishment of HIE models is equivalent to the first stage of clinical HIE pathological and physiological development, and 6-9 hours is equivalent to the second stage, and after 9 hours is equivalent to the third stage. Therefore, before 3 hours is the best time window for intervention and treatment of neonatal HIE rat models.

Key words: HIE model, hypoxia ischemia, brain injury, pathological changes, acute phase

摘要： 目的　通过建立新生SD大鼠缺氧缺血性脑损伤(HIE)模型,分析急性期脑组织病理变化。方法　收集甘肃 省妇幼保健院(甘肃省中心医院)54例新生儿重度HIE患儿CT影像学资料,对脑损伤部位进行分析,对24只新生 儿7日龄SD大鼠建立HIE动物模型,分别在建模后1、3、6、9 h取其脑组织,通过TTC、HE、Nissl染色及流式技术, 分析缺血面积、丘脑、皮层、海马组织病理、细胞氧化应激及凋亡和坏死变化。结果　重度HIE患儿丘脑受到的影 响最大;动物造模后1~3 h右侧丘脑LDDM、LDVL区、皮层S1BF、M2、RSA及海马CA1区神经元细胞形态发生变 化,染色逐渐变浅,细胞数量逐渐减少;3~6 h各区域染色越来越浅,细胞形态变化及数量减少明显,同时皮层S1BF 逐渐出现缺血坏死;6~9 h各区域组织形态及细胞数量变化更加明显,ROS开始升高。结论　HIE动物模型造模后 3~6 h相当于临床HIE病理生理发展的第一阶段,6~9 h相当于第二阶段,9 h以后相当于第三阶段,因此3 h以前 是新生HIE大鼠模型干预治疗的最佳时间窗。

关键词: HIE模型, 缺氧缺血, 脑损伤, 病理变化, 急性期