新生猪缺氧缺血性脑病模型的建立

A model of hypoxic-ischemic encephalopatby in the neonatal piglets

目的建立一种新生猪缺氧缺血性脑病（HIE）模型。方法健康3～7d雄性新生猪随机分为假手术组（Sham n=5）和模型组（HI n=12），采用全身缺氧40min、空气5min、窒息7min后复氧、心肺复苏再灌注法制作新生猪HIE模型，于自主循环恢复（ROSC）后第4天取脑，观察缺血缺氧后小猪体质量增长情况，神经功能障碍评分（NDS）以及脑组织病理形态学改变。结果两组各参数基础值差异无统计学意义，HI组在40min缺氧过程中，氧分压降至（22±3）mmHg，心率加快，平均动脉压升高，动脉氧饱和度降低，血糖升高；吸入空气时上述参数略有恢复；在7min窒息期间，表现更严重的低氧血症、代谢性酸中毒、高碳酸血症、高血糖以及显著的低血压和心动过缓，窒息5min时MABP降至（30±18）mmHg；HI组体质量增长明显慢于Sham组（P〈0．05）。Sham组除第1天因麻醉残留造成较高的NDS评分外，后期未见明显异常行为改变，HI组ROSC后第1、2和3天NDS评分明显升高（P〈0．05）。Sham组脑神经元形态正常，HI组壳核、尾状核和感觉运动皮层存活神经元密度分别降低至Sham组的（12．6±10．1）％、（51．5±8．4）％和（49．1±23．4）％（P〈0．01）。结论制作新生猪HIE模型成功，该模型符合新生儿围产期全身缺氧、窒息继发缺血，复氧、CPR后再灌注致HIE脑损伤病理生理变化过程。纹状体和感觉运动皮层HE染色可见以核固缩为典型特征的神经元缺血性改变.

Objective To duplicate a model of hypoxic-ischemic eneephalopathy （HIE） in the neonatal piglets and discuss the relative issues about the model. Methods A total of 17 3-7 day healthy male piglets were randomly divided into 2 groups：sham group （n =5） ,and HI group （n = 12）. The HIE model was produced by hypoxia 40 min, room air 5 min, asphyxia 7 min and followed by reopen oxygen, CPR until ROSC. The brains were collected when the piglets were survived 4 days. Neurological deficit score （NDS） and histologic changes were studied in each group. Results There were no differences in physiologic parameters on baseline between two groups. HI group had arterial O2 desaturation, arterial hypertension, and tachycardia during the 40 min period of hypoxia and light recovery during the 5 min period of room air ventilation. During the 7 min period of asphyxia, HI groups exhibited more severe degrees of hypoxia,severe acidosis, hypercapnia, hyperglycemia, hypotension, and bradycardia. The weight in the HI group was increased obviously slower than that in sham group （ P 〈 0.05 ）. There were no abnormal behaviors in sham group except day 1 showing a higher NDS due to anesthesia. The NDS was significantly increased in the HI group at day 1,2 and 3 after ROSC （ P 〈 0.05 ）. Neurons were normal in sham group. The density of viable neurons in HI group was decreased to （ 12.6 ± 10. 1 ） % in putamen, （ 51.5 ± 8.4）% in caudate and （49.1 ±23.4）% in sensorimotor cortex of sham group （P 〈0.01）. Conclusion This model of HIE is successful. Systemic hypoxia followed by asphyxic cardiac arrest is well characterized physiologically and pathologically, and the pattern of brain injury closely resembles human newborn HI encephalopathy.