雄激素对缺氧缺血性脑损伤新生大鼠脑组织芳香化酶和神经生长因子表达的影响

Effects of androgen on the expression of brain aromatase cytopigment and nerve growth factor in neonatal rats with hypoxic-ischemic brain damage

摘要:

目的：观察雄激素对缺氧缺血性脑损伤（HIBD）新生大鼠皮质及海马区芳香化酶细胞色素P450（AROM）与神经生长因子（NGF）表达及脑组织超微结构的影响，探讨雄激素的神经保护作用机制。方法：96只7日龄Sprague-Dawley大鼠随机分为假手术组、HIBD组和雄激素组，每组32只。雄激素组和HIBD组制作HIBD模型。缺氧缺血（HI）后两组动物分别给予腹腔注射丙酸睾丸酮(25 mg/kg)和等量的花生油。于HI后24 h、72 h、7 d、10 d观察各组海马和皮层神经元超微结构变化及AROM和NGF表达的变化。结果：电镜下可见HIBD组神经细胞水肿，细胞器减少，核肿胀，染色质凝集成块状，线粒体减少、肿胀，可见大量凋亡细胞。与HIBD组相比，雄激素干预组神经细胞排列较整齐，神经元核膜完整，染色质均匀, 细胞凋亡少见，神经元轴突再生明显。HIBD组HI后24 h NGF与AROM表达出现阳性反应，HI后72 h 明显增多，7 d达高峰，10 d后开始下降，但仍高于假手术组。雄激素组皮层和海马NGF与AROM的表达在HI后72 h、7 d 和10 d 明显高于HIBD组和假手术组，均有统计学意义（P<0.01）。结论：雄激素干预可增加脑组织NGF和AROM的表达，促进神经细胞形态的恢复及神经元轴突再生，减少细胞凋亡，具有明显的神经保护作用。

Abstract:

ObjectiveTo study the effects of androgen on the expression of aromatase cytopigment P450 (AROM) and nerve growth factor (NGF) in the brain and brain ultrastructure in neonatal rats with hypoxic-ischemic brain damage (HIBD) in order to investigate the mechanism underlying the protective effect of androgen against HIBD. MethodsNinty-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and androgen treatment (n=32 each). HIBD was induced by the ligation of left common carotid artery and hypoxia exposure. The rats in the androgen treatment and the HIBD groups were injected intraperitoneally with testosterone propionate (25 mg/kg) and arachis oil respectively immeadiatedly after hypoxia-ischemia (HI). After 24 and 72 hrs and 7 and 10 days of HI, AROM and NGF expression in the cortex and the hippocampus was detected with the immunohistochemical method. The ultrastructural changes of neurons in the cortex and the hippocampus were observed under a transmission electron microscope. ResultsNerve cells of the HIBD group showed obvious injuries including cell organ decreasing, cellularoedema, nuclear swelling, chromatic agglutination, mitochondria decreasing and swelling, as well as an increase in apoptotic cells. Compared with the HIBD group, the nerve cells in the androgen treatment group had integrated nuclear membrane, well-distributed chromatin and abundant cell organs, and less cell apoptosis and increased axon regeneration. There was a positive expression of NGF and AROM in the brain cortex and the hippocampus in the HIBD group 24 hrs after HI. The expression of NGF and AROM increased significantly 72 hrs after HI, peaked 7 days after HI and then began to decrease but remained at a higher level than that in the sham-operation group 10 days after HI. The NGF and AROM expression in the cortex and the hippocampus in the androgen treatment group was significantly higher than that in the sham-operation and the HIBD groups 72 hrs, and 7 and 10 days after HI.ConclusionsAndrogen treatment can promote axon regeneration and morphous recovery of nerons and decrease neural apoptosis in neonatal rats with HIBD. The neuroprotection of androgen is produced possibly through an increase in the expression of NGF and AROM in the brain.