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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。
BACKGROUND: Traumatic brain injury can stimulate the proliferation of neural stem cells to some extent. However, progesterone improves learning and memory after traumatic brain injury. Progesterone may promote the recovery of neural function by stimulating the proliferation of neural stem cells. Objective: To observe the effect of progesterone on the proliferation of neural stem cells after diffuse brain injury. Design: Randomized controlled animal experiments. Unit: Xinxiang Medical College. MATERIALS: Forty-eight adult male Sprague Dawley rats aged 45 months and weighing 280-330 g were used. Methods: The experiment was performed in Xinxiang Medical College from September 2004 to February 2005. Marmarou diffuse brain injury model was used. 48 rats were randomly divided into 4 groups, 12 in each group: ① sham operation group, only incision scalp suture. ② brain trauma group, the establishment of brain trauma animal model. ③ dimethylsulfoxide group, intracerebroventricular injection of dimethyl sulfoxide equivalent volume of progesterone group 1h and after traumatic brain injury. ④ progesterone group, intracerebroventricular injection of progesterone 4mg / kg 1h and after traumatic brain injury. Animals were killed at 3 and 6 days after sham operation or traumatic brain injury. Morphological changes of neurons in cerebral cortex were observed by hematoxylin-eosin staining. Expression of hippocampus and dentate gyrus protein was detected by immunohistochemical staining. MAIN OUTCOME MEASURES: Morphological observation of neurons; detection of hippocampal and dentate gyrus nestin expression. Results: ① There was no neuron injury in cortex of rats in sham-operation group, cortex of rats in 3d and 6d after traumatic brain injury showed obvious neuron damage, with neuron loss, both neurons in progesterone 3d group and 6d group Obviously lighter than brain injury group. ② The dentate gyrus protein in sham-operated group showed low or slight expression, and the expression of nestin in hippocampal CA4 region was occasionally observed. The expression of CA4 and dentate gyrus protein in hippocampus of traumatic brain injury group was significantly increased (P <0.05). Compared with traumatic group, the expression of CA4 and dentate nestin in hippocampus of rats in trabeculectomy group was significantly increased (P <0.05) . ③ There was no significant difference between neuron injury and nestin expression in brain injury group and dimethylsulfoxide group (P> 0.05). Conclusion: Progesterone can reduce the traumatic brain injury may be related to its promotion of neural stem cell proliferation.