金刚烷胺对创伤性脑损伤幼鼠行为学及脑内TH表达的影响  

Effect of amantadine on traumatic brain injury induced young mice behavior and the expression of TH

作　　者：吴宇[1] 刘阳[2] 唐素林[1] 宋亮[2] 陈幽婷[2] 马传响[2] 

机构地区：[1]徐州医学院江苏省麻醉与镇痛应用技术重点实验室,徐州221000 [2]徐州医学院人体解剖学教研室,徐州221000

出　　处：《神经解剖学杂志》2014年第1期103-108,共6页Chinese Journal of Neuroanatomy

摘　　要：目的:探讨金刚烷胺(amantadine,AMA)长期注射对创伤性脑损伤(traumatic brain injury,TBI)幼鼠脑内酪氨酸羟化酶(tyrosine hydroxylase,TH)的影响,为深入探讨AMA药理学效应和指导临床儿童颅脑外伤的治疗提供实验学依据。方法:昆明幼年小鼠(P10)80只,性别不拘,随机分为对照组、AMA组、TBI组及TBI+AMA组。TBI模型在第10 d(P10)应用自由落体重力打击制作成轻中度闭合型TBI模型,再连续给药10 d,停药后第10 d(P30)进行自发活动观察和被动回避性跳台实验检测;其中停药后第1 d(P21)和第3 d(P23)取脑;应用Western blot技术检测前脑内相关脑区TH的含量变化;应用冰冻切片的免疫组织化学染色技术检测小鼠脑内酪氨酸羟化酶(TH)的表达变化。结果:(1)行为学检测:旷场实验中,AMA组和TBI组幼鼠自发活动均明显低于对照组(P<0.05),但TBI+AMA组幼鼠自发活动增加,与TBI组的差别有统计学意义(P<0.05)。被动回避性跳台实验中,AMA组与对照组之间的差别无统计学意义(P>0.05),但TBI组比对照组幼鼠学习记忆时间明显延长,差别有统计学意义(P<0.05);TBI+AMA组与TBI组幼鼠学习记忆能力无明显改变。(2)Western Blot结果显示:AMA组幼鼠杏仁核+杏仁周皮质、前额皮质内TH蛋白的含量在1 d时高于对照组(P<0.05),3 d时AMA组与对照组之间TH蛋白含量的差异无统计学意义(P>0.05)。TBI+AMA组幼鼠隔区和前额皮质TH蛋白的含量在1 d时高于TBI组(P<0.05),3 d时仅TBI+AMA组隔区TH蛋白含量高于TBI组(P<0.05)。(3)免疫组织化学染色结果显示:TBI+AMA组幼鼠黑质、腹侧被盖区、蓝斑的TH阳性神经元数量明显高于TBI组,光密度值分析两组间差异有统计学意义(P<0.05)。结论:AMA长期注射可提高TBI幼鼠脑内杏仁核和前额皮质等脑区多巴胺的浓度,进而改善创伤性脑损伤幼鼠的行为学症状。Objective： To explore the effect of amantadine （AMA） on the traumatic brain injury （traumatic brain inju- ry, TBI） mice brain dopamine system by long-term injection, and to probe the pharmacological effect of AMA and provid experimental scientific basis. Methods： Kunming young mice 80 （P10）, either sex were randomly divided into four groups ： （ 1 ） control group, （2） AMA group, （3） TBI group, （4） TBI ＋ AMA group （ traumatic brain injury model ＋ AMA, 30 mg/kg, ip × 10 d）. The free fall against gravity was used to set up closure type with mild to moderate TBI model on the tenth days and injection for ten days. After discontinuation of 10 d （1930） , spontaneous activity and passive avoidance behavior of jumping experimental testing was observed. Withdrawal after 1 d （ P21 ） and 3 d （ P23 ）, the brain was removed. The content of TH change in the related brain areas was tested by Western blot technique; the tyrosinehydroxylase （TH） expression changes in mouse brain was observed by immunohistochemistry. Results： （1）Behavioral detection ： in open-field experiments, the spontaneous activity of mice in AMA and TBI groups was significantly lower than the control group （ P 〈 O. 05 ）, but the spontaneous activity of mice in TBI ＋ AMA group increased and the difference was statistically significance compared with TBI group （ P 〈 0.05 ）. In step down passive avoidance sexual experiments, AMA group and control group had no significant difference （ P 〉 0.05 ）, but the learning and memory of mice in TBI group was significantly longer than the control group, the difference was statistically significant （ P 〈 0.05 ）. The learning and mem- ory in rats TBI ＋ AMA group and the TBI group in did not change significantly. （2） Western Blot results showed that in the amygdala ＋ almond weeks cortex, prefrontal cortex in AMA group, TH protein content in 1 d group were higher than the control group （P 〈 0.05 ）. At 3 d,TH protein content

关 键 词：金刚烷胺 创伤性脑损伤 酪氨酸羟化酶 幼鼠 

分 类 号：R651.15[医药卫生—外科学]