补肝养髓方对自发老年性痴呆模型神经信使分子一氧化氮代谢的影响

Effect of bugan yangsui formula on the metabolism of nitric oxide as nerve messenger molecule in mice with spontaneous senile dementia

目的:观察补肝养髓方对自发老年性痴呆模型学习记忆功能及神经信使分子一氧化氮代谢的影响。方法:从21月龄昆明种小鼠筛选出自发老年性痴呆(记忆障碍)鼠,随机分为4组即空白对照组、hydergine对照组、补肝养髓小剂量组、补肝养髓大剂量组、另设老年学习记忆正常组(简称正常对照组,下同)。hyderglne对照组给以Hydergine0.6mg/kg,补肝养髓小、大剂量组分别予补肝养髓方天泰1号6.80g/kg及20.41g/kg,连续60d,正常对照和痴呆对照组均灌以等量DW;用跳台实验(step-downtest)检测学习记忆成绩;脑组织冷冻切片,NBT组织化学法示大脑神经元型一氧化氮合酶(NOS1)活性,全自动显微图像象分析系统定量。结果:天泰1号能显著改善自发老年性痴呆模型小鼠的学习记忆障碍(P<0.05～0.01),并明显增强中枢大脑皮质和海马NOS1活性及其纤维密度(P<0.05～0.01),其作用呈现出一定的量效关系。此外,研究还发现颞叶皮质、海马NOS1活性与学习记忆成绩呈显著性正相关(相关系数为0.877,0.965,P<0.01)。结论:中枢NOS1活性与学习记忆成绩显著相关;补肝养髓方可明显改善自发老年性痴呆模型的学习记忆障碍。

AIM:To observe the effect of bugan yangsui formula on the cognitive and learning function and metabolism of nitric oxide(NO) as nerve messenger molecule in mice model with spontaneous senile dementia. METHODS:Spontaneous senile dementia(memory retention disorder) mice were screened out from 21 months old Kunming mice and then were divided randomly into 4 groups:blank control group,Hydergine control group,bugan yangsui formula groups,including low dosage group and high dosage group,and normal control group(with aged mice in normal learning and cognitive function).Hydergine control group was treated with Hydergine at the dosage of 0.6 mg/kg,while low dosage group and high dosage group were treated with bugan yangsui formula Tiantai No.1 at the dosage of 6.80 g/kg and 20.41 g/kg respectively for 60 days.Normal control and blank group were treated with equal volume DW.The ability of learning and memory was tested with step down test. Brain tissue was made to frozen section and the activity of nitric oxide synthase(NOS1) was shown with NBT histochemical technique.Automatic micro image analysis system was used to determine quantitatively. RESULTS:Tiantai No.1 could improve the disorder of learning and memory in mice with spontaneous senile dementia significantly(P< 0.05-0.01),and enhance the activity and fiber density of NOS1 in the central cerebral cortex and hippocampus(P< 0.05-0.01).All these effects had a dose effct relationship.Furthermore,the results showed that the activity of NOS1 in temporal lobe cortex and hippocampus had remarkably positive correlation with the ability of learning and memory(with the correlation coefficient of 0.877 and 0.965 respectively,P< 0.01). CONCLUSION:The activity of NOS1 in central nervous system has significantly close correlation with the ability of learning and memory;bugan yangsui formula can improve the disorder of learning and memory in mice model with spontaneous senile dementia significantly.