中文摘要：

目的制作并鉴定研究足月新生儿缺氧缺血性脑损伤（HIBD）的大鼠模型,以期用于足月新生儿缺氧缺血性脑损伤发病机制及治疗的研究。方法40只新生10日龄SD大鼠分为对照组18只和实验组（HIBD组）22只,实验组行右侧颈总动脉结扎,缺氧（8%氧和92%氮气）2.5 h;对照组只分离右侧颈总动脉,不行结扎和缺氧处理。应用Longa评分法评价神经行为学改变;HE染色检测组织病理学改变;免疫组化检测凋亡标志蛋白cleavedcaspase-3（CC3）的表达;及TUNEL染色检测细胞凋亡情况。结果对照组大鼠全部存活,实验组死亡4只,死亡率18.1%。Longa评分分析实验组有不同程度神经功能缺损,与对照组比较差异有显著性（P〈0.05）;HE染色显示实验组均出现脑组织充血、水肿,缺血侧更重,细胞体肿胀,细胞排列紊乱,结构不清;免疫组化显示实验组CC3表达随损伤时间延长逐渐增加,与对照组比较差异有显著性（P〈0.01）;TUNEL染色显示实验组阳性细胞随时间延长逐渐增加,与对照组比较差异有显著性（P〈0.05）。结论该大鼠模型脑组织病变符合足月新生儿HIBD的病理学改变及神经行为学改变,可用于足月新生儿HIBD发病机制与防治措施的研究。

英文摘要：

Objective To establish an animal model mimicking neurobehavioral characteristics and pathological changes in term human neonates with hypoxic-ischemic brain damage（HIBD）,and thus to study the pathophysiological mechanisms and therapies in term neonates with HIBD.Methods Postnatal day 10 SD rats underwent hypoxic-ischemic（experimental group） or sham（control） treatment.For both groups,each rat was anesthetized with ethylether.In the experimental group,the right common carotid artery of rats was ligated and exposed to hypoxia in a chamber filling with 8% oxygen（balanced with nitrogen） for 2.5 h.For the sham control,the right common carotid artery was surgically exposed,but not ligated or exposed to hypoxia.Longa score was used to assess the neuropathology.Rat brains were collected at 4 h,8 h and 24 h after treatment.HE staining was used to detect neuronal pathological changes.The apoptotic marker,cleaved caspase-3（CC3） protein,was detected with immunohistochemistry.TUNEL method was used to detect apoptosis.Results Cell swelling,necrosis,and rarefaction were observed in the experimental group but not in the sham control group by HE staining.The expression of CC3 protein as well as the TUNEL positive cells were expressed at 4 h and peaked at 24 h after hypoxia-ischemia in the experimental rats,which was significantly higher compared to that in the sham control group（P0.01）.There were different degrees of neurological impairment in the experimental group.The Longa Score was significantly higher compared to that in the sham control group（P0.01）.Conclusion The neurobehavioral characteristics and pathological changes in this rat model are consistent with the changes in term human neonatal HIBD.Therefore,this model can be used to study pathophysiological mechanisms and therapies for term human neonatal HIBD.