摘要
背景:神经元型一氧化氮(NO)与突触可塑性有关,为正常学习记忆的关键递质。神经元型一氧化氮合酶(nNOS)是神经元内NO的生物合成酶。阿尔茨海默病(AD)患者大脑nNOS活性特别是颞叶皮质和海马CA1区nNOS阳性神经纤维的变化尚少见报道。目的:观察自发老年性痴呆模型大脑nNOS活性特别是颞叶皮质和海马CA1区nNOS阳性神经纤维的变化,并观察天泰1号对其nNOS活性的影响。设计:随机对照的实验研究。单位:深圳市中西医结合研究所。材料:实验在深圳市中西医结合研究所二级动物实验室完成。实验动物为65只昆明种小鼠。方法:实验动物饲养至21个月龄,按国际通用标准和方法从老龄动物中筛选老年性痴呆小鼠;实验动物随机分为4组即老年痴呆组、西药对照组、天泰1号小剂量组、天泰1号大剂量组、另设老年学习记忆正常组(简称老年正常组,下同),每组13只。西药对照组给以Hydergine0.6mg/kg,天泰1号小、大剂量组分别予天泰1号6.80g/kg及20.41g/kg,连续60d,老年正常和老年痴呆组均灌以等量双蒸水;用跳台实验(step-downtest)检测学习记忆成绩;脑组织冷冻切片,NBT组织化学法示大脑nNOS活性,全自动显微图像分析系统定量。主要观察指标:①天泰1号不同剂量对自发老年性痴呆鼠学习记忆的影响。②大脑nNOS活性的检测。
BACKGROUND:Neuron nitrogen monoxide(NO) is related to synaptic plasticity and is the key transmitter of normal learning and memory.Neuronal nitric oxide synthase(nNOS) is the biological synthetic enzyme of NO in neurons.The reports have been fewer yet on cerebral nNOS activity in Alzheimer disease(AD) patients,especially on changes in positive neural fibers of nNOS in temporal lobe cortex and hippocapmus CA1 region.OBJECTIVE:To observe cerebral nNOS activity in AD patients, especially on changes in positive neural fibers of nNOS in temporal lobe cortex and hippocapmus CA1 region and effects of Tiantai Ⅰon nNOS activity.DESIGN:A randomized and controlled trial.SETTING:Institute of Collaboration of Chinese and Western Medicine, Shenzhen City.MATERIALS:The experiment was performed in No.2 Grade Animal Experimental Room of Institute of Collaboration of Chinese and Western Medicine,Shenzhen City.A total of 65 Kunming mice were employed in the experiment.METHODS:The experimental animals were bred till 21 months old and the mice with senile dementia were screened from the aged ones according to the international general standards and methods.The experimental animals were randomized into 4 groups,named as senile dementia group,western drug control,group with small dosage of Tiantai Ⅰand group with large dosage of Tiantai Ⅰ.In addition,a group with normal learning and memory of the senile mice(simply called senile normal group) was designed.There were 13 mice in each group.In western drug control,hydergine 0.6 mg/kg was prescribed; in the groups of small and large dosage of Tiantai Ⅰ,the dosages were 6.80 g/kg and 20.41 g/kg respectively,continuously for 60 days.In senile normal group and senile dementia group,the bi distilled water of equal dosage was applied for perfusion.The scores of learning and memory were determined by step down test. Slices of brain tissues were prepared with frozen,nNOS activity was displayed by NBT histochemistry method and the analysis was done systematically with auto micrography in quantity.MAIN OUTCOME MEASURES:①Effects of Tiantai Ⅰon learning and memory of mice with spontaneous senile dementia.②Determination of nNOS activity in cerebrum.RESULTS:Learning and memory were significantly decreased in mice with senile dementia(P< 0.01),the positive reaction of nNOS was remarkably weaker compared with normal aged mice.It was the first time to discover that the surface densities of nNOS positive neural fibers in temporal lobe cortex and hippocampus CA1 region [(9.48±2.09),(5.11±2.74) respectively]were remarkably lower than those of the normal aged mice [(17.75±3.47),(11.95±2.00) respectively](P< 0.01).Simultaneously, it was also the first time to discover that normal correlation was apparent between nNOS activity of cortex and hippocampus and the scores of learning and memory.Tiantai Ⅰcould significantly increase the surface densities of nNOS positive neural fibers in cortex and hippocampus in senile dementia mice, of which, the values of the small dosage were (11.57±2.44) and (8.18±2.92) respectively and of the large dosage were (12.59±2.88) and (9.33±2.18) respectively,(P< 0.01-0.05).CONCLUSION:The hypo activity of central nNOS in senile dementia mice resulted in significantly decreased positive neural fibers of nNOS in cerebral cortex and hippocampus.The surface densities of nNOS positive neural fibers in temporal lobe cortex and hippocampus CA1 region were significantly related to the scores of learning and memory.Tiantai Ⅰcould remarkably improve the disturbance of learning and memory in spontaneous senile dementia model and enhance its nNOS activity in cerebral cortex and hippocampus.
出处
《中国临床康复》
CSCD
北大核心
2005年第4期244-247,共4页
Chinese Journal of Clinical Rehabilitation
