黄体酮对大鼠脑创伤后神经干细胞增殖的影响

背景:脑创伤一定程度上可刺激神经干细胞增殖,而黄体酮可改善脑创伤后学习记忆功能,黄体酮可能通过刺激神经干细胞增殖,促进脑创伤后神经功能的恢复。目的:观察黄体酮对弥漫性脑创伤后神经干细胞增殖的影响。设计:随机对照动物实验。单位:新乡医学院。材料:成年健康雄性SD大鼠48只,四五个月龄,体质量280～330g。方法:实验于2004-09/2005-02在新乡医学院完成。采用Marmarou弥漫性脑创伤模型。48只大鼠随机分为4组,每组12只:①假手术组,仅切开头皮后缝合。②脑创伤组,建立脑创伤动物模型。③二甲基亚砜组,脑创伤后1h及以后每天腹腔注射与黄体酮组等容量的二甲基亚砜。④黄体酮组,脑创伤后1h及以后每天腹腔注射黄体酮4mg/kg。于假手术或脑创伤手术后3,6d处死动物,苏木精-伊红染色观察大脑皮质神经元形态学变化,免疫组织化学染色检测海马和齿状回巢蛋白表达情况。主要观察指标:神经元组织形态学观察;海马和齿状回巢蛋白表达检测。结果:①假手术组大鼠皮质无神经元损伤,脑创伤3d组和6d组大鼠皮质显示明显的神经元损伤,有神经元缺失,黄体酮3d组和6d组所显示的神经元损伤均明显轻于脑创伤组。②假手术组齿状回巢蛋白呈低水平或少量表达,海马CA4区偶见巢蛋白表达。脑创伤组海马CA4区和齿状回巢蛋白表达则明显增多(P<0.05),黄体酮组大鼠海马CA4区和齿状回巢蛋白的表达与脑创伤组比较明显增多(P<0.05)。③脑创伤组和二甲基亚砜组在神经元损伤和巢蛋白表达方面无明显差别(P>0.05)。结论:黄体酮减轻脑创伤作用可能与其促进神经干细胞增殖有关。

Effects of progesterone on the proliferation of neural stem cells in rats with brain trauma

BACKGROUND: Brain trauma can stimulate the proliferation of neural stem cells (NSCs) to some extent, while progesterone can ameliorate the learning and memory function following brain trauma, which can also promote the neurofunctional recovery after brain trauma by stimulating the proliferation of NSCs.OBJECTIVE: To observe the effects of progesterone on the proliferation of NSCs after diffuse brain injury (DBI).DESIGN: Randomized control animal experiment.SETTING: Xinxiang Medical College.MATERIALS: Forty-eight healthy male SD rats at 4-5 months with the body mass of 280-330 g were selected.METHODS: The experiment was conducted in Xinxiang Medical College from September 2004 to January 2005. Forty-eight rat models of Marmarou DBI were selected and randomly divided into 4 groups with 12 rats in each group: ①Sham-operation group: rats were cut open the scalp and then sutured.②Brain trauma group: rats were made into animal models of brain trauma.③Dimethyl sulphoxide (DMSO) group: rats were given intraperitoneal injection of DMSO at the same volume as progesterone group at one hour after brain trauma and then the same administration was performed daily. ④Progesterone group: rats were intraperitoneally injected with 4 mg/kg progesterone at one hour after brain trauma and then the same administration was performed daily. Rats were executed respectively at 3 and 6 days after sham operation or brain trauma operation, and hematoxylin-eosin staining was conducted to observe the morphological changes of cortical neurons in brain. The expressions of nestin in dentate gyrus and hippocampus were detected with immunohistochemical staining.MAIN OUTCOME MEASURES: Observation of histomorphological changes of neurons and detection of the expressions of nestin in hippocampus and dentate gyrus.RESULTS: ①There was no injury in cortical neurons in the sham-operation group, while obvious neuronal injury and loss in cortex of rats were found in the 3-day and 6-day brain trauma groups, and the neuronal injury was significantly severer in brain trauma than in 3-day and 6-day progesterone groups. ②The expressions of nestin in hippocampal CA4 region or dentate gyrus of sham-operation group were in low level or little, and the expression of nestin could be seen occasionally in hippocampal CA4 region. The expressions of nestin in hippocampal CA4 region and dentate gyrus of the brain trauma group significantly increased (P ＜ 0.05), while those in the progesterone group increased more than the brain trauma group remarkably (P ＜ O.05).③There were no differences in neuronal injury and nestin expression between braintrauma group and DMSO group(P ＞ 0.05).CONCLUCION: Progesterone for brain trauma may be related with its promoting effects on the proliferation of NSCs.