新生大鼠缺氧缺血脑组织水肿及水通道蛋白-4的表达变化

目的 探讨新生SD大鼠缺氧缺血不同时间点脑组织水肿及水通道蛋白-4 (AQP-4) 表达的功能意义。 方法 健康3 d龄SD大鼠60只, 分为对照组 (12只) 和缺氧缺血脑损伤模型 (HIBD)组 （48只)。HIBD 组行右侧颈总动脉结扎后,分为吸入80 mL/L O2+920 mL/L N2 4 h、8 h、16 h、24 h 四个亚组，每组12只大鼠。对照组仅行假手术, 不予右颈总动脉结扎和缺氧缺血。HIBD各亚组分别于持续缺氧缺血4 h、8 h、16 h、24 h后处死动物,对照组于手术后12 h处死。取脑组织分别进行HE染色观察脑组织病理改变、脑含水量测定、实时荧光定量PCR检测大脑海马AQP-4 mRNA表达。 结果 HE染色示:随着缺氧缺血时间延长，右脑神经细胞与胶质细胞肿胀进行性加重,24 h组神经细胞溶解损伤明显，胶质细胞稀疏变性。HIBD 组右侧大脑持续缺氧缺血8 h、16 h和24 h脑组织含水量均较对照组增加, 差异有统计学意义 (P<0.05);实时荧光定量PCR显示右脑海马AQP-4 mRNA表达较对照组减少 (P<0. 05)。 结论 新生大鼠缺氧缺血后脑组织水肿，海马AQP-4表达下调，提示AQP-4与脑组织水肿有关。

Changes on the Expression of Aquaporin-4 is Associated with Edema of Brain in Neonatal Rats Subjected toHypoxic Ischemic Brain Damage

Objective To investigate changes of Aquaporin-4 (AQP-4) and the relation of brain edema after different time of hypoxic ischemic brain damage (HIBD). Methods Healthy 3 day-old SD rats (n=60), were divided into Sham group (n=12), the hypoxic ischemic brain damage group (n=48). The rats were subjected to the ligation of right carotid artery (ischemia). After rewarming 30 min with mother, they were sent into a box full with 80 mL/L oxygen and 920 mL/L nitrogen (hypoxia) for 4 h, 8 h, 16 h, 24 h (n=12 respectively). The rats of sham group were subjected to exposure right carotid artery, but were not ligated. Rats of the HIBD group were sacrificed at 4 h, 8 h, 16 h, 24 h of hypoxic ischemic damage and rats of the sham group were sacrificed at 12 h after operation without hypoxic ischemic damage. Then brain water content from left and right hemisphere were investigated respcetively to observe brain edema at different time of hypoxic ischemic brain damage, which was followed by the investigation of brain pathology through HE staining. Real time PCR was used to test the level of AQP-4 mRNA. Results Water content of right brain increased significantly after 8 h, 16 h and 24 h hypoxic ischemic brain damage, compared with the sham group (P<0.05). Under light microscopy, the size of neurons and glia cells increased gradually during 8-24 h following HIBD. Dissolved Neurons were obviously observed during 16-24 h of HIBD. Glia cells were scarcely distributed. The mRNA expression of AQP-4 in right hippocampus decreased significantly during 4-24h of HIBD by evaluated with real time PCR (P<0.05), when compared with the sham group. Conclusion AQP-4 mRNA expression in hippocampus of neonatal rats with HIBD exhibited a significant decrease, which was associated with brain edema. The present findings indicated that AQP-4 may has a novel role in the brain edema in neonatal rats with HIBD.