Li Xiaojuan, Bai Ruiying, Zhang Junhe, Wang Xiaoyin
Department of Physiology and Neurobiology, Xinxiang Medical University Xinxiang 453003, China.
Department of Biochemistry and Molecular Biology, Xinxiang Medical University Xinxiang 453003, China.
Int J Clin Exp Med. 2015 Oct 15;8(10):18831-6. eCollection 2015.
To observe the effect of progesterone (PROG) on blood-brain barrier (BBB) permeability, brain tissue water content and dynamic changes of aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischaemic brain damage (HIBD). 72 neonatal Wistar rats, aged 7 days old, were randomly divided into control, hypoxic-ischaemic (6, 24 and 72 h, and 7 d subgroups) and drug groups (6, 24 and 72 h, and 7 d subgroups). The HIBD animal model was established. BBB was detected via an Evans blue tracer. Brain water content was determined by the dry/wet method. The AQP-4 expression in the cerebral cortex was observed through immunohistochemistry and Western blot. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the hypoxia-ischaemia group were significantly higher than those of the control group after hypoxia for 6 h (P < 0.05), continued to rise within 24 h and then reached the peak at 72 h. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the drug group were significantly lower than those of the hypoxia-ischaemia group after hypoxia for 6, 24 and 72 h (P < 0.05). Moreover, BBB permeability and BBB expression were positively correlated with the AQP-4 expression. In conclusion, PROG protects the brain of HIBD neonatal rats by alleviating the damage of BBB and cerebral oedema. The protective effect of PROG may be related to the down-regulation of AQP-4 expression in the cerebral cortex of neonatal rats.
观察孕酮（PROG）对缺氧缺血性脑损伤（HIBD）新生大鼠血脑屏障（BBB）通透性、脑组织含水量及水通道蛋白4（AQP-4）动态变化的影响。将72只7日龄新生Wistar大鼠随机分为对照组、缺氧缺血组（6、24、72小时及7天亚组）和药物组（6、24、72小时及7天亚组）。建立HIBD动物模型。通过伊文思蓝示踪剂检测BBB。采用干湿法测定脑组织含水量。通过免疫组织化学和蛋白质印迹法观察大脑皮质中AQP-4的表达。缺氧缺血组新生大鼠大脑皮质的BBB通透性、脑组织含水量及AQP-4表达在缺氧6小时后显著高于对照组（P<0.05），24小时内持续升高，72小时达到峰值。药物组新生大鼠大脑皮质的BBB通透性、脑组织含水量及AQP-4表达在缺氧6、24和72小时后显著低于缺氧缺血组（P<0.05）。此外，BBB通透性和BBB表达与AQP-4表达呈正相关。综上所述，PROG通过减轻BBB损伤和脑水肿来保护HIBD新生大鼠的大脑。PROG的保护作用可能与新生大鼠大脑皮质中AQP-4表达的下调有关。
