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孕酮干预对缺氧缺血性脑损伤中AQP-4动态变化的影响

Effect of progesterone intervention on the dynamic changes of AQP-4 in hypoxic-ischaemic brain damage.

作者信息

Li Xiaojuan, Bai Ruiying, Zhang Junhe, Wang Xiaoyin

机构信息

Department of Physiology and Neurobiology, Xinxiang Medical University Xinxiang 453003, China.

Department of Biochemistry and Molecular Biology, Xinxiang Medical University Xinxiang 453003, China.

出版信息

Int J Clin Exp Med. 2015 Oct 15;8(10):18831-6. eCollection 2015.

Abstract

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.

摘要

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。

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