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目的通过对3日龄大鼠缺氧缺血(HI)处理制备脑损伤动物模型,探讨HI对大鼠脑室周围白质神经细胞凋亡及其对未成熟大鼠远期脑发育的影响。方法完成实验的112只3日龄SD大鼠,雌雄不限,随机分为实验组和对照组各56只。实验组大鼠结扎右侧颈总动脉,HI后予60 mL·L-1氧气、940 mL·L-1氮气处理4 h。对照组仅分离右侧颈总动脉,不予结扎和缺氧处理。HI后12 h、24 h、48 h、72 h、7 d、14 d及28 d各组处死8只大鼠,观察脑组织病理变化,脱氧核糖核苷酸转移酶介导的缺口末端标记法观察大鼠神经细胞凋亡情况,HI后28 d对大鼠进行行为能力测定。结果实验组大鼠在HI过程中及HI完成后均有躁动、反应差等异常表现,体质量增长明显慢于对照组。实验组HI 12 h时可见细胞形态和细胞器结构变化,细胞凋亡、坏死;7 d可见胼胝体变薄;14 d可见少突胶质细胞减少,胞体萎缩;28 d可见髓鞘萎缩,稀疏,有坏死灶。实验组凋亡细胞数HI 12 h时开始增加,3 d达峰值,7 d开始下降,14 d、28 d恢复正常;各时间点差异有统计学意义(F=12.868,P<0.05);与对照组比较,HI 12 h、24 h、3 d、7 d凋亡细胞百分比均显著升高(Pa<0.05),14 d、28 d差异无统计学意义(Pa>0.05);实验组大鼠28 d悬吊实验、斜坡实验均较对照组减退。结论 HI可导致大鼠脑白质神经细胞凋亡增加,并影响其远期智能发育。
Objective To investigate the effects of HI on the apoptosis of periventricular white matter neurons and their effect on the long-term brain development in immature rats by hypoxia-ischemia (HI) treatment on 3-day-old rats. Methods One hundred and twelve 3-day-old SD rats were randomly divided into experiment group and control group (n = 56). Rats in the experimental group were ligated to the right common carotid artery, 60 mL · L -1 oxygen was administered to HI and 4 h nitrogen was treated with 940 mL·L -1 nitrogen. The control group only isolated the right common carotid artery, not ligation and hypoxia. Eight rats were sacrificed at 12 h, 24 h, 48 h, 72 h, 7 d, 14 d and 28 d after HI, respectively. Pathological changes of brain tissue were observed. Deoxyribonucleotide transferase mediated nick end labeling The apoptosis of nerve cells in rats was observed, and the behavioral ability of rats was measured 28 days after HI. Results Rats in the experimental group had agitation and poor response during HI and HI, and the body weight gain was significantly slower than that of the control group. The morphology and organelle structure change of the experimental group was observed at 12 h after HI. The apoptosis and necrosis of the corpus callosum were observed on the 7th day. The corpus callosum became thinner on the 7th day. The oligodendrocyte decreased and the cell body atrophy was found on the 14th day. Necrosis. The number of apoptotic cells in experimental group began to increase at 12 h, reached the peak at 3 d, decreased at 7 d, returned to normal at 14 d and 28 d, and the difference was statistically significant at each time point (F = 12.868, P <0.05) Compared with the control group, the percentages of apoptotic cells in HI at 12 h, 24 h, 3 d and 7 d were significantly increased (P <0.05), but no significant difference at 14 and 28 d (P> 0.05) 28 d suspension experiment, slope experiment than the control group decreased. Conclusion HI can increase the apoptosis of rat white matter neurons and affect their long-term intelligent development.