Department of Cardiothoracic Surgery, Heart Center, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Cardiothoracic Surgery, Shenzhen Children's Hospital, Shenzhen, China.
J Thorac Cardiovasc Surg. 2020 Aug;160(2):e55-e66. doi: 10.1016/j.jtcvs.2020.03.057. Epub 2020 Apr 4.
This study aims to evaluate the protective effects of progesterone on white matter injury and brain immaturity in neonatal rats with chronic hypoxia.
Three-day old Sprague-Dawley rats were randomly divided into 3 groups: (1) control (n = 48), rats were exposed to normoxia (fraction of inspired oxygen: 21% ± 0%); (2) chronic hypoxia (n = 48), rats were exposed to hypoxia (fraction of inspired oxygen: 10.5% ± 1.0%); and (3) progesterone (n = 48), rats were exposed to hypoxia and administrated with progesterone (8 mg/kg/d). Hematoxylin-eosin staining, immunohistochemistry, real-time quantitative polymerase chain reaction, and Western blot analyses were compared on postnatal day 14 in different groups. Motor skill and coordination abilities of rats were assessed via rotation experiments.
Increased brain weights (P < .05), narrowed ventricular sizes (P < .01), and rotarod experiment scores (P < .01) were better in the progesterone group than in the chronic hypoxia group. The number of mature oligodendrocytes and myelin basic protein expression increased in the progesterone group compared with the chronic hypoxia group (P < .01). The polarization of M1 microglia cells in the corpus callosum of chronic hypoxia-induced hypomyelination rats was significantly increased, whereas there were fewer M2 microglia cells. Conversely, progesterone therapy had an opposite effect and caused an increase in M2 microglia polarization versus a reduction in M1 microglia cells.
Progesterone could prevent white matter injury and improve brain maturation in a neonatal hypoxic rat model; this may be associated with inducing a switch from M1 to M2 in microglia.
本研究旨在评估孕激素对慢性缺氧新生大鼠脑白质损伤和脑不成熟的保护作用。
将 3 日龄 Sprague-Dawley 大鼠随机分为 3 组：（1）对照组（n=48），大鼠暴露于常氧环境（吸入氧分数：21%±0%）；（2）慢性缺氧组（n=48），大鼠暴露于低氧环境（吸入氧分数：10.5%±1.0%）；（3）孕激素组（n=48），大鼠暴露于低氧环境并给予孕激素（8mg/kg/d）。在不同组别的第 14 天，进行苏木精-伊红染色、免疫组织化学、实时定量聚合酶链反应和 Western blot 分析。通过旋转实验评估大鼠的运动技能和协调能力。
与慢性缺氧组相比，孕激素组的脑重增加（P<.05），脑室缩小（P<.01），转棒实验评分升高（P<.01）。孕激素组成熟少突胶质细胞数量和髓鞘碱性蛋白表达增加（P<.01）。慢性缺氧诱导的少突胶质细胞脱髓鞘大鼠胼胝体 M1 型小胶质细胞极化明显增加，而 M2 型小胶质细胞减少。相反，孕激素治疗有相反的效果，导致 M2 型小胶质细胞极化增加而 M1 型小胶质细胞减少。
孕激素可预防新生缺氧大鼠的脑白质损伤，促进脑成熟；这可能与小胶质细胞 M1 向 M2 的转化有关。
