Li Xiaojuan, Zhang Junhe, Zhu Xiaoqian, Hou Ruanling, Li Xinjuan, Dong Xianhong, Wang Xiaoyin, Lu Chengbiao
Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Exp Ther Med. 2014 May;7(5):1311-1316. doi: 10.3892/etm.2014.1589. Epub 2014 Feb 27.
Progesterone (PROG) has been shown to exhibit a protective function against hypoxic-ischemic brain damage. The aim of the present study was to study the effects of PROG in a neonatal rat model of hypoxic-ischemic brain injury. A total of 30 Wistar rats, aged 7 days, were randomly divided into three groups: Sham, model and PROG. The rats in the model and PROG groups underwent a left common carotid artery ligation and were placed in a sealed container at 37°C with 8% O and 92% N gas mixtures for 2.5 h to establish animal models of hypoxic-ischemic encephalopathy. The rats in the PROG group were intraperitoneally treated with 8 mg/kg PROG solution 30 min prior to the induction of hypoxia-ischemia. All animals were sacrificed after 24 h and neuronal changes were observed with electron microscopy to investigate the hypoxic-ischemic brain damage. The protein and mRNA expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus were detected by immunohistochemistry and quantitative polymerase chain reaction, respectively. The results revealed that the neuronal structures in the sham group were normal. The neuronal structures in the model group exhibited cavitation changes, but these were reduced following PROG administration. The protein and mRNA expression levels of TNF-α and NF-κB in the hippocampal neurons were increased in the model group, and pretreatment with 8 mg/kg PROG was shown to reduce the expression levels of these inflammatory mediators. Therefore, PROG was shown to exert an important protective function in hypoxic-ischemic brain injury by inhibiting the cascade of inflammatory injury induced by TNF-α and NF-κB.
黄体酮（PROG）已被证明对缺氧缺血性脑损伤具有保护作用。本研究的目的是研究PROG在新生大鼠缺氧缺血性脑损伤模型中的作用。总共30只7日龄的Wistar大鼠被随机分为三组：假手术组、模型组和PROG组。模型组和PROG组的大鼠进行左侧颈总动脉结扎，并置于37°C、含8%氧气和92%氮气混合气体的密封容器中2.5小时，以建立缺氧缺血性脑病动物模型。PROG组的大鼠在诱导缺氧缺血前30分钟腹腔注射8mg/kg的PROG溶液。24小时后处死所有动物，用电子显微镜观察神经元变化，以研究缺氧缺血性脑损伤。分别通过免疫组织化学和定量聚合酶链反应检测海马中肿瘤坏死因子-α（TNF-α）和核因子-κB（NF-κB）的蛋白质和mRNA表达水平。结果显示，假手术组的神经元结构正常。模型组的神经元结构出现空泡化改变，但PROG给药后这些改变减少。模型组海马神经元中TNF-α和NF-κB的蛋白质和mRNA表达水平升高，8mg/kg PROG预处理可降低这些炎症介质的表达水平。因此，PROG通过抑制TNF-α和NF-κB诱导的炎症损伤级联反应，在缺氧缺血性脑损伤中发挥重要的保护作用。
